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  • Comparison of bone structure and microstructure in the metacarpal heads between patients with psoriatic arthritis and healthy controls: an HR-pQCT study
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-14
    D. Wu, J.F. Griffith, S.H.M. Lam, P. Wong, J. Yue, L. Shi, E.K. Li, I.T. Cheng, T.K. Li, V.W. Hung, L. Qin, L.-S. Tam

    Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH.

    更新日期:2020-01-15
  • Effect of vitamin D on bone strength in older African Americans: a randomized controlled trial
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-14
    R. Dhaliwal, S. Islam, M. Mikhail, L. Ragolia, J.F. Aloia

    Abstract Summary There is controversy over whether African Americans have higher vitamin D requirements than recommended by the Institute of Medicine. We previously reported that maintaining serum 25(OH)D above 30 ng/mL does not prevent age-related bone loss. Herein, we report that bone strength is also unaffected by maintaining this level in this population. Introduction The role of vitamin D in bone strength has not been investigated in the African American (AA) population. Methods A 3-year randomized controlled trial was designed to examine the effect of vitamin D supplementation on physical performance, bone loss, and bone strength in healthy older AA women. A total of 260 postmenopausal AA women, ages ≥ 60 years were randomized to a vitamin D3 or placebo arm. Vitamin D3 dose was adjusted to maintain serum 25OHD > 30 ng/mL. Bone mineral density, femoral axis length, and femoral neck (FN) width were measured by dual-energy X-ray absorptiometry. Composite indices of FN strength [compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI)] were computed. Results The mean age of participants was 68.2 ± 4.9 years. Baseline characteristics between groups were similar. The average dose of vitamin D3 was 3490 ± 1465 IU/day in the active group. The mean serum 25OHD was 46.8 ± 1.2 ng/mL versus 20.7 ± 1.1 ng/mL in the active versus placebo group. Serum 25OHD did not correlate with any composite indices. The longitudinal differences observed in FN width, CSI, BSI, and ISI in both groups were not statistically significant (all p values > 0.05). Further, there was no group × time interaction effect for any of the composite indices (all p values > 0.05). Conclusion Maintaining serum 25OHD > 30 ng/mL (75 nmol/L) does not affect bone strength in older AA women. There is no evidence to support vitamin D intake greater than the recommended RDA by the Institute of Medicine in this population for bone strength.

    更新日期:2020-01-14
  • Incidental bilateral calcaneal fractures following overground walking with a wearable robotic exoskeleton in a wheelchair user with a chronic spinal cord injury: is zero risk possible?
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-13
    A. Bass, S.N. Morin, M. Vermette, M. Aubertin-Leheudre, D.H. Gagnon

    Many individuals with spinal cord injury (SCI) rely on wheelchairs as their primary mode of locomotion leading to reduced weight-bearing on the lower extremities, which contributes to severe bone loss and increased risk of fragility fractures. Engaging in a walking program may reverse this vicious cycle, as this promotes lower extremity weight-bearing and mobility, which may reduce bone loss and fragility fracture risk. However, fragility fracture risk associated with the use of wearable robotic exoskeletons (WREs) in individuals with SCI needs consideration. A 35-year-old man with chronic complete sensorimotor SCI (neurological level = T6) and low initial bone mineral density enrolled in a 6- to 8-week WRE-assisted walking program after successfully completing an initial clinical screening process and two familiarization sessions with the WRE. However, after the first training session with the WRE, he developed bilateral localized ankle edema. Training was suspended, and a CT-scan revealed bilateral calcaneal fractures, which healed with conservative treatment over a 12-week period. Opportunities for improving clinical screening and WRE design are explored. The relevance of developing clinical practice guidelines for safe initiation and progression of intensity during WRE-assisted walking programs is highlighted. This case of bilateral calcaneal fractures illustrates that aiming for “zero risk” during WRE-assisted walking programs may not be realistic. Although WREs are a relatively new technology, current evidence confirms their potential to greatly improve health and quality of life in individuals with chronic SCI. Hence, ensuring their safe use remains a key priority.

    更新日期:2020-01-14
  • Increased rate of reoperation in atypical femoral fractures is related to patient characteristics and not fracture type. A nationwide cohort study
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-13
    H.P. Bögl, K. Michaëlsson, G. Zdolsek, J. Höijer, J. Schilcher

    Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type.

    更新日期:2020-01-14
  • Correction to: Impact of whole dairy matrix on musculoskeletal health and aging–current knowledge and research gaps
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-13
    N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli, Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup

    The article Impact of whole dairy matrix on musculoskeletal health and aging–current knowledge and research gaps written by N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli,Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup.

    更新日期:2020-01-13
  • Incidence of distal radius fracture in a general population in southern Sweden in 2016 compared with 2001
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-13
    M. Ali, A. Eiriksdottir, M. Murtadha, A. Åkesson, I. Atroshi

    Abstract Summary In this population-based study, we compared the incidence of distal radius fracture in 2016 with that in the same region’s adult general population in 2001 using radiographs to identify fracture cases. We showed that the incidence decreased by 24% in 2016 compared with 2001 indicating an important development. Introduction We conducted an epidemiological study on residents of northeastern Skåne in southern Sweden (population 182,000) to determine the overall incidence of distal radius fracture and the incidence according to age, sex, and fracture characteristics in the region’s adult population during 2016, and to study the change in incidence in the same general population between 2001 and 2016 using wrist radiographs to identify fracture cases. Methods Two orthopedic surgeons examined all wrist radiographs performed at the only two emergency hospitals in the study region to identify individuals, above 18 years of age, who sustained fracture of the distal radius during 2016. We used Poisson regression analysis adjusting for age, sex, and at-risk population to compare the incidence in 2016 with the incidence in 2001, previously estimated using similar methodology. Results The overall incidence in 2016 was 22 (95% CI 20–25) per 10,000; the incidence in women was 34 (95% CI 30–39) and in men was 10 (95% CI 8–12) per 10,000. The overall incidence in 2016 was 0.76 (95% CI 0.70–0.82) of the incidence in 2001 (p < 0.0001). The incidence in the 3 age groups 19–49, 50–79, and ≥ 80 years was 0.91 (95% CI, 0.69–1.20), 0.67 (95% CI, 0.55–0.82), and 0.49 (95% CI, 0.25–0.97) of the incidence in 2001, respectively. Conclusion In a general population in Sweden, a statistically significant and clinically important decrease in the incidence of distal radius fracture occurred between 2001 and 2016, driven by lower incidence in individuals 50 years or older.

    更新日期:2020-01-13
  • Adherence to fracture liaison service programs in patients over 70: the hidden part of the iceberg
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-11
    B. Mugnier, A. Daumas, S. Doddoli, S. Belmeliani, A.-L. Couderc, B. Mizzi, P. Lévêque, P. Villani

    Abstract Summary Significant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence. Introduction FLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70. Methods Our multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program. Results About half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned. Conclusion We observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

    更新日期:2020-01-13
  • Bone microstructure and volumetric bone mineral density in patients with hyperuricemia with and without psoriasis
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-10
    D. Simon, J. Haschka, C. Muschitz, A. Kocijan, A. Baierl, A. Kleyer, G. Schett, S. Kapiotis, H. Resch, M. Sticherling, J. Rech, R. Kocijan

    We analyzed volumetric bone mineral density (vBMD) and bone microstructure using HR-pQCT in subjects with normouricemia (NU) and subjects with hyperuricemia (HU) with and without psoriasis (PSO). HU was associated with higher cortical vBMD and thickness. Differences in average and trabecular vBMD were found between patients with PSO + HU and NU.

    更新日期:2020-01-11
  • Effects of a resistance and balance exercise programme on physical fitness, health-related quality of life and fear of falling in older women with osteoporosis and vertebral fracture: a randomized controlled trial
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-10
    B. Stanghelle, H. Bentzen, L. Giangregorio, A.H. Pripp, D. Skelton, A. Bergland

    Abstract Summary Exercise is recommended for people with osteoporosis, but the effect for people who have suffered vertebral fracture is uncertain. This study shows that a multicomponent exercise-program based on recommendations for people with osteoporosis improved muscle strength, balance, and fear of falling in older women with osteoporosis and vertebral fracture. Introduction Guidelines for exercise strongly recommend that older adults with osteoporosis or osteoporotic vertebral fracture should engage in a multicomponent exercise programme that includes resistance training in combination with balance training. Prior research is scarce and shows inconsistent findings. This study examines whether current exercise guidelines for osteoporosis, when applied to individuals with vertebral fractures, can improve health outcomes. Methods This single blinded randomized controlled trial included 149 older women diagnosed with osteoporosis and vertebral fracture, 65+ years. The intervention group performed a 12-week multicomponent exercise programme, the control group received usual care. Primary outcome was habitual walking speed, secondary outcomes were physical fitness (Senior Fitness Test, Functional Reach and Four Square Step Test), health-related quality of life and fear of falling. Descriptive data was reported as mean (standard deviation) and count (percent). Data were analyzed following intention to treat principle and per protocol. Between-group differences were assessed using linear regression models (ANCOVA analysis). Results No statistically significant difference between the groups were found on the primary outcome, walking speed (mean difference 0.04 m/s, 95% CI − 0.01–0.09, p = 0.132). Statistically significant between-group differences in favour of intervention were found on FSST (dynamic balance) (mean difference − 0.80 s, 95% CI − 1.57 to − 0.02, p = 0.044), arm curl (mean difference 1.55, 95% CI 0.49–2.61, p = 0.005) and 30-s STS (mean difference 1.85, 95% CI 1.04–2.67, p < 0.001), as well as fear of falling (mean difference − 1.45, 95% CI − 2.64 to − 0.26, p = 0.018). No statistically significant differences between the groups were found on health-related quality of life. Conclusion Twelve weeks of a supervised multicomponent resistance and balance exercise programme improves muscle strength and balance and reduces fear of falling, in women with osteoporosis and a history of vertebral fractures. Trial registration ClincialTrials.gov Identifier: NCT02781974. Registered 25.05.16. Retrospectively registered.

    更新日期:2020-01-11
  • Low volumetric bone density is a risk factor for early complications after spine fusion surgery
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-09
    Y. Liu, A. Dash, A. Krez, H. J. Kim, M. Cunningham, F. Schwab, A. Hughes, B. Carlson, A. Samuel, E. Marty, H. Moore, D. J. McMahon, J. A. Carrino, R. S. Bockman, E. M. Stein

    This study aims to investigate lumbar spine (LS) volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion.

    更新日期:2020-01-09
  • No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-04
    E.D. Alten, A. Chaturvedi, M. Cullimore, A.A. Fallon, L. Habben, I. Hughes, N.T. O’Malley, H. Rahimi, D. Renodin-Mead, B.L. Schmidt, G.A. Weinberg, D.R. Weber

    Scurvy, due to vitamin C deficiency, is commonly referenced as a “forgotten” or “historical” disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases.

    更新日期:2020-01-04
  • Comparison of the clinical effectiveness and safety between the use of denosumab vs bisphosphonates in renal transplant patients
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-03
    H. McKee, G. Ioannidis, A. Lau, D. Treleaven, A. Gangji, C. Ribic, M. W. Pack, A. Papaioannou, J. D. Adachi

    A retrospective chart review was conducted on 85 renal transplant patients aged 19–88 years, treated with denosumab or bisphosphonate therapy. Bone densitometry measures were compared between treatment groups at baseline; at years 1, 2, and 3; and at final follow-up (average of 3.4 years).

    更新日期:2020-01-04
  • Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-03
    M. L. Bouxsein, P. Zysset, C. C. Glüer, M. McClung, E. Biver, D.D. Pierroz, S. L. Ferrari

    Abstract Summary We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment. Introduction The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies. Methods We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment. Results Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available. Conclusions Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

    更新日期:2020-01-04
  • How does women’s bone health recover after lactation? A systematic review and meta-analysis
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-02
    F. M. F. Grizzo, A. C. J. Alarcão, C. M. Dell’ Agnolo, R. B. Pedroso, T. S. Santos, J. R. N. Vissoci, M. M. Pinheiro, M. D. B. Carvalho, S. M. Pelloso

    Abstract Mini abstract This is a systematic review aiming to evaluate the recovery of bone mass after lactation-related loss. Bone loss is transitory with recovery depending on the return of menstruation and weaning, and several compensatory homeostatic mechanisms are involved to minimize any significant damage to the maternal skeleton. Abstract Lactation has been associated with significant temporary bone loss, especially during the exclusive breastfeeding period. In the bone recovery phase, there is wide methodological heterogeneity among clinical trials, including follow-up timing, methods and sites of bone measurements, and body composition changes. The purpose of this study is to perform a systematic review and meta-analysis aiming to evaluate the recovery rate of bone mass after lactation-related loss, including the PubMed, Web of Science, and Scopus databases, with no publication date restrictions. The following MeSH terms were used: “bone diseases,” “bone resorption,” “bone density,” “osteoporosis,” “calcium,” “postpartum period,” “weaning,” “breast feeding,” and “lactation.” The inclusion criteria were as follows: prospective human studies in women of reproductive age and bone measurements with two assessments in the postpartum period at least: the first one within the first weeks of lactation and another one 12 months after delivery, 3 months following the return of menses or 3 months postweaning. This research was recorded on the Prospero database (CRD42018096586Bone). A total of 9455 studies were found and 32 papers met the inclusion criteria. The follow-up period ranged from one to 3.6 years postpartum. Lactation was associated with transient bone loss, with a strong tendency to recover in all the sites studied, depending on the return of menstruation and weaning. Small deficits in the microarchitecture of the peripheral skeleton may be present, especially in women with prolonged breastfeeding, but with no deficit regarding the hip geometry was found. Women with a successive gestation after prolonged lactation and women who had breastfed when adolescents had no significant bone loss. Bone loss related to lactation is transitory, and several compensatory homeostatic mechanisms are involved to minimize any significant damage to the maternal skeleton.

    更新日期:2020-01-04
  • An 11-year review of hip fracture hospitalisations, health outcomes, and predictors of access to in-hospital rehabilitation for adults ≥ 65 years living with and without dementia: a population-based cohort study
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-02
    R. Mitchell, B. Draper, H. Brodaty, J. Close, H.P. Ting, R. Lystad, I. Harris, L. Harvey, C. Sherrington, I.D. Cameron, J. Braithwaite

    Abstract Summary This study examined hip fracture hospitalisation trends and predictors of access to rehabilitation for adults aged ≥ 65 years living with and without dementia. The hospitalisation rate was 2.5 times higher for adults living with dementia and adults who lived in aged care were between 4.8 and 9.3 times less likely to receive rehabilitation. Introduction To examine hip fracture hospitalisation temporal trends, health outcomes, and predictors of access to in-hospital rehabilitation for older adults living with and without dementia. Methods A population-based retrospective cohort study of adults aged ≥ 65 years hospitalised with a hip fracture during 2007–2017 in New South Wales, Australia. Results Of the 69,370 hip fracture hospitalisations, 27.1% were adults living with dementia. The hip fracture hospitalisation rate was 2.5 times higher for adults living with dementia compared with adults with no dementia (1186.6 vs 492.9 per 100,000 population). The rate declined by 6.1% per year (95%CI − 6.6 to − 5.5) for adults living with dementia and increased by 1.0% per year (95%CI 0.5–1.5) for adults with no dementia. Multivariable associations identified that adults living with dementia who experienced high frailty and increasing age were between 1.6 and 1.8 times less likely to receive in-hospital rehabilitation. Adults who were living in long-term aged care facilities were between 4.8 and 9.3 times less likely to receive in-hospital rehabilitation which varied by the presence of dementia or delirium. Conclusion Consistent criteria should be applied to determine rehabilitation access, and rehabilitation services designed for older adults living with dementia or in aged care are needed. Highlights • Adults living with dementia were able to make functional gains following hip fracture rehabilitation. • Need to determine consistent criteria to determine access to hip fracture rehabilitation. • Rehabilitation services specifically designed for adults living with dementia or in aged care are needed.

    更新日期:2020-01-04
  • Real-world impact of glucocorticoid replacement therapy on bone mineral density: retrospective experience of a large single-center CAH cohort spanning 24 years
    Osteoporos. Int. (IF 3.819) Pub Date : 2020-01-02
    L. L. Iervolino, B. Ferraz-de-Souza, R. M. Martin, F. C. Costa, M. C. Miranda, B. B. Mendonça, T. S. Bachega

    Abstract Summary The congenital adrenal hyperplasia population seems to have an intrinsic tendency to a high frequency of low bone mass. However in this single-center and long-term evaluated cohort, the simplified corticoid regimen, with exclusive dexamethasone single dose reposition during adulthood, did not represent a risk factor for decrease in bone health. Introduction The impact of long-term and supposedly physiological doses of gluco and mineralocorticoid (GC/MC) on bone mineral density (BMD) in congenital adrenal hyperplasia (CAH) remains discordant among studies, which contain different clinical forms and corticoid regimens. Our aim was to evaluate the BMD in CAH adults receiving similar GC regimen since childhood and to correlate it with GC/MC cumulative doses. Methods Only patients with good compliance, who used cortisone acetate (CA) during childhood and dexamethasone after the final height achievement. Cumulative GC/MC doses were calculated from diagnosis until last evaluation. BMD was analyzed by the first and last energy X-ray absorptiometry (DXA) scans performed. Results Twenty simple virilizing (SV) and 14 salt wasting (WS) whose mean age was 26 ± 6 years, mean CA, dexamethasone, and fludrocortisone cumulative doses were 63,813 ± 32,767, 812 ± 558, and 319 ± 325 mg/m2, respectively. Based on the last DXA, low BMD was observed in 11% of patients, total hip Z-score was lower in the SW than SV form (p = 0.04). Cumulative CA dose had an inverse correlation with femoral neck Z-score (p < 0.01). Total cumulative GC and MC doses had an inverse correlation with total hip Z-score (p < 0.01). In the analysis of sequential BMD during dexamethasone therapy, no association was observed among cumulative GC/MC doses, clinical forms, sex, and lumbar Z-score delta. Conclusions Even though a low CA regimen during growth periods in addition to MC replacement appears to have an influence on BMD at femoral sites, interestingly a low dexamethasone one does not seem to be deleterious for bone health in adulthood.

    更新日期:2020-01-04
  • Higher fracture prevalence and smaller bone size in patients with hEDS/HSD—a prospective cohort study
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-24
    T. Banica, M. Coussens, C. Verroken, P. Calders, I. De Wandele, F. Malfait, H.-G. Zmierczak, S. Goemaere, B. Lapauw, L. Rombaut

    Increased fracture risk in patients with Ehlers-Danlos syndromes has been reported, but the reasons for it are incompletely understood. We aimed to investigate possible determinants of this increased risk and found that hEDS/HSD patients present with a cortical bone size deficit compared with control subjects, possibly related to lower mechanical loading.

    更新日期:2020-01-04
  • Modification of the RANKL-RANK-binding site for the immunotherapeutic treatment of osteoporosis
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-20
    Y. Ko, G. Lee, B. Kim, M. Park, Y. Jang, W. Lim

    Here, we proposed the use of mutated RANKL as an immunogen for active immunization and to induce anti-cytokine antibodies for osteoporosis treatment.

    更新日期:2020-01-04
  • A fall in the previous 12 months predicts fracture in the subsequent 5 years in postmenopausal women
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-19
    N. Afrin, R. Sund, R. Honkanen, H. Koivumaa-Honkanen, T. Rikkonen, L. Williams, H. Kröger

    The purpose of this study was to evaluate if a history of falls predicts future postmenopausal fractures and if this prediction variesaccording to frequency, mechanism, and severity of falls and site of fractures.

    更新日期:2020-01-04
  • Management of Paget’s disease of bone
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-17
    I.R. Reid

    Paget’s disease is a progressive focal bone condition which can result in pain, low quality of life, deformity and other complications. Disease progression can be halted with potent bisphosphonates, resulting in improvement in both quality of life and pain, and normalisation of scintigraphy, plain radiographs and bone histology. Zoledronate has transformed the treatment of Paget’s disease, producing sustained remissions in almost all patients. Thus, it is now possible to normalise bone cell activity and prevent disease progression at low cost, with one or two intravenous injections of zoledronate, greatly reducing follow-up costs. Patients with Paget’s disease who are symptomatic or at risk of complications should have the opportunity to reap these therapeutic benefits.

    更新日期:2020-01-04
  • Postmenopausal women with osteoporosis consume high amounts of vegetables but insufficient dairy products and calcium to benefit from their virtues: the CoLaus/OsteoLaus cohort
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-17
    A. Lanyan, P. Marques-Vidal, E. Gonzalez-Rodriguez, D. Hans, O. Lamy

    Abstract Summary We evaluated the associations between nutrients, dietary patterns or compliance to dietary guidelines and bone health among postmenopausal women from the CoLaus/OsteoLaus cohort. Postmenopausal women with osteoporosis consume a high amount of vegetables but insufficient amount of dairy products and calcium to benefit from their adherence to dietary guidelines. Introduction Diet plays a significant role in the prevention of osteoporosis (OP). We evaluated the associations between nutrients, dietary patterns or compliance (expressed in odds of meeting) to dietary Swiss guidelines and bone health (T score < − 2.5 SD, TBS < 1230) among postmenopausal women. Methods One thousand two hundred fifteen women (64.3 ± 7.5 years) from the CoLaus/OsteoLaus cohort (Lausanne, Switzerland) had their dietary intake assessed using a validated food frequency questionnaire. Bone mineral density (BMD), trabecular bone score (TBS) and vertebral fractures were evaluated with DXA. OP risk factors, calcium supplements (> 500 mg) and prevalent major OP fractures were assessed by questionnaire. Results One hundred eighty of 1195 women had OP according to BMD, 87/1185 a low TBS and 141/1215 prevalent major OP fractures. In multivariate analysis (adjusted for total energy intake, age, antiosteoporotic treatment, educational level, BMI, sedentary status and diabetes), OP women consumed more vegetable proteins (21.3 ± 0.4 vs 19.6 ± 0.2 g/day), more fibres (18.2 ± 0.5 vs 16.5 ± 0.2 g/day), less animal proteins (40.0 ± 1.1 vs 42.8 ± 0.4 g/day), less calcium (928 ± 30 vs 1010 ± 12 mg/day) and less dairy products (175 ± 12 vs 215 ± 5 g/day), all p ≤ 0.02. According to guidelines, OP women had a tendency to higher compliance for vegetables (OR (95% CI) 1.50 (0.99–2.26)) and a lower compliance for dairy (OR (95% CI) 0.44 (0.22–0.86)) than those without OP. Women taking calcium supplements consumed significantly higher amounts of dairy products. No association was found between TBS values or prevalent OP fractures and any dietary components. Conclusion Postmenopausal women with OP consume a high amount of vegetables but insufficient amount of dairy products and calcium. TBS does not seem to be influenced by diet.

    更新日期:2020-01-04
  • Comparison of multimedia and printed patient education tools for patients with osteoporosis: a 6-month randomized controlled trial
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-16
    M.A. Lopez-Olivo, J.K.A. des Bordes, H. Lin, T. Rizvi, R.J. Volk, M.E. Suarez-Almazor

    We conducted a randomized controlled trial to compare the efficacy of adding a video tool to a printed booklet on osteoporosis. Both strategies were effective in increasing knowledge and decreasing decisional conflict. There was no difference in the measured outcomes between the intervention and control groups. Patient preferences and learning styles are key factors in deciding a presentation format when educating patients with osteoporosis.

    更新日期:2020-01-04
  • Fracture prevention by screening for high fracture risk: a systematic review and meta-analysis
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-14
    T. Merlijn, K.M.A. Swart, H.E. van der Horst, J.C. Netelenbos, P.J.M. Elders

    Abstract This systematic review and meta-analysis showed a significant reduction of (major) osteoporotic fractures and hip fractures after screening using fracture risk assessment and bone densitometry compared with usual care. The results indicate that screening is effective for fracture risk reduction, especially hip fractures. To perform a systematic review and meta-analysis of population screening for high fracture risk on fracture prevention compared with usual care. MEDLINE and Embase were searched for studies published until June 20th 2019. Randomized studies were selected that screened for high fracture risk using at least bone densitometry, screened in a general population, provided subsequent treatment with anti-osteoporosis medication, had a usual care group as comparator, and had at least one fracture-related outcome (all fractures, (major) osteoporotic fractures, or hip fractures). The primary assessment was the hazard ratio (HR) for fracture-related outcomes. All-cause mortality was a secondary outcome. Random-effects models were used to estimate pooled HRs. We identified 1186 potentially eligible articles and included three randomized studies: the ROSE study, the SCOOP study, and the SOS with a total number of N = 42,009 participants. Respectively, 11%, 15%, and 18% of the participants in the intervention group started medication. Meta-analysis showed a statistically significant and clinically relevant reduction of osteoporotic fractures (HR = 0.95, 95% confidence interval (CI) = 0.89–1.00), major osteoporotic fractures (HR = 0.91; 95%CI = 0.84–0.98), and hip fractures (HR = 0.80; 95%CI = 0.71–0.91), but no reduction of all fractures (HR = 0.95; 95%CI = 0.89–1.02). The pooled HR for the secondary outcome all-cause mortality was 1.04 (95% CI = 0.95–1.14). Numbers needed to screen to prevent one fracture were 247 and 272 for osteoporotic fractures and hip fractures, respectively (corresponding to 113 and 124 performed bone densitometry examinations, and 25 and 28 persons being treated). This meta-analysis showed that population screening is effective to reduce osteoporotic fractures and hip fractures. Implementation of screening in older women should be considered as serious option to prevent osteoporotic fractures, especially hip fractures.

    更新日期:2020-01-04
  • Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-14
    G. Tsvetov, O. Amitai, T. Shochat, I. Shimon, A. Akirov, T. Diker-Cohen

    Abstract Summary Hypocalcemia was reported at low rates (0.05–1.7%) in denosumab-treated postmenopausal women with osteoporosis. This real-life study shows a 7.4% rate of denosumab-induced hypocalcemia in community-dwelling osteoporotic men and women. Pretreatment serum calcium and creatinine levels are major predictors for this complication. Serum-calcium monitoring may help to identify and prevent severe hypocalcemia. Purpose RCTs have reported a 0.05–1.7% rate of hypocalcemia in denosumab-treated postmenopausal women with osteoporosis, but long-term real-life data are lacking. We assessed the rate of hypocalcemia in osteoporotic community-dwelling patients treated with denosumab. Methods A retrospective analysis was conducted based on medical records (2010–2018) from a large HMO. An albumin-adjusted serum calcium concentration lower than 8.5 mg/dL was defined as hypocalcemia. Results We included 2005 patients (93% women, mean age 76 ± 9 years). Hypocalcemia developed during treatment in 149 patients (7.4%; 1% less than 8 mg/dL): in 66 after 0.5–1 years; 48 after 1–2 years; 35 after > 2 years. On comparison of the hypocalcemic and normocalcemic patients, the strongest predictors of hypocalcemia were pretreatment levels of albumin-adjusted serum calcium (9.1 ± 0.4 vs. 9.4 ± 0.5 mg/dL, respectively; p < 0.05) and creatinine (0.9 ± 0.5 vs. 0.8 ± 0.3 mg/dL, respectively; p < 0.05). The hypocalcemia rate increased in parallel to a decrease in eGFR (p = 0.032 for the difference between eGFR ranges). Baseline calcium level ≤ 9.31 mg/dL predicted hypocalcemia with a sensitivity of 77% and specificity of 56%. A model of (− 2)*calcium + creatinine predicted hypocalcemia (3.7% when lower and 17.1% when higher than − 17.4). Gender, age, 25-hydroxyvitamin-D, parathyroid hormone, alkaline phosphatase, and whether denosumab was given as first or advanced line of osteoporotic therapy had no predictive value. Conclusion Real-life rates of denosumab-induced hypocalcemia are higher than previously reported. Hypocalcemia might develop after each dose of denosumab in ongoing treatment. Adequate calcium and vitamin D supplementation are needed. Serum calcium monitoring is advised in high-risk patients for early detection of severe hypocalcemia.

    更新日期:2020-01-04
  • Diabetes and fractures: new evidence of atypical femoral fractures?
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-14
    N.H. Rasmussen, J. Dal, F. de Vries, J.P. van den Bergh, M.H. Jensen, P. Vestergaard

    Patients with diabetes have an increased risk of fractures. In this study, subtrochanteric and femoral shaft fractures were increased in patients with type 1 diabetes compared with the general population. In the light of this, more evidence points towards an association between diabetes and atypical femoral fractures.

    更新日期:2020-01-04
  • Patient engagement in clinical guidelines development: input from > 1000 members of the Canadian Osteoporosis Patient Network
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-14
    S. N. Morin, M. Djekic-Ivankovic, L. Funnell, L. Giangregorio, I. B. Rodrigues, R. Ridout, S. Feldman, S. Kim, H. McDonald-Blumer, G. Kline, W. E. Ward, N. Santesso, W. D. Leslie

    Patient engagement in clinical guidelines development is essential. The results of a self-administered online survey identified themes important to people living with osteoporosis and will inform the development of Osteoporosis Canada clinical guidelines recommendations.

    更新日期:2020-01-04
  • Increased risk for hip fracture after death of a spouse—further support for bereavement frailty?
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-12
    C. H. Vala, M. Lorentzon, V. Sundh, H. Johansson, C. Lewerin, S. Sten, M. Karlsson, C. Ohlsson, B. Johansson, J. A. Kanis, D. Mellström

    Death of a spouse is associated with poorer physical and mental health. We followed all married individuals, born from 1902 to 1942, during the period from 1987 to 2002, and found that widows and widowers had higher risk for hip fracture, compared with still married women and men.

    更新日期:2020-01-04
  • Risk for hip fracture before and after total knee replacement in Sweden
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-12
    C.H. Vala, J. Kärrholm, J.A. Kanis, H. Johansson, S. Sten, V. Sundh, M. Karlsson, M. Lorentzon, D. Mellström

    Abstract Summary We studied the risk for hip fracture before and after total knee replacement (TKR) in the entire population in Sweden. Women and men had a low risk for hip fracture before TKR but an increased risk the first year after TKR. Purpose It is known that osteoarthritis is associated with high bone mass. We therefore studied the risk of hip fracture before and after total knee replacement (TKR), risk of different hip fracture types, and risk subdivided in genders and age groups. Methods We followed the total Swedish population born between 1902 and 1952 (n = 4,258,934) during the period 1987–2002 and identified all patients with TKR due to primary OA (n = 39,291), and all patients with hip fracture (n = 195,860) in the Swedish National Inpatient Register. The risk time analyses were based on Poisson regression models. Results The hazard ratio (HR) for hip fracture the last year before TKR was 0.86 (95% CI 0.74 to 1.00) and the first year after 1.26 (95% CI 1.11 to 1.42) compared to individuals without TKR. The HR for femoral neck fracture 0–10 years after TKR was 0.95 (95% CI 0.89 to 1.01) and for trochanteric fracture was 1.13 (95% CI 1.06 to 1.21). The HR for hip fracture in the age group 50–74 was 1.28 (95% CI 1.14 to 1.43) and in the age group 75–90 years was 0.99 (95% CI 0.94 to 1.04) 0–10 years after TKR, compared to individuals without TKR. Conclusion Individuals had a low risk for hip fracture before TKR but an increased risk the first year after TKR. The risk in individuals below age 75 years and for trochanteric fractures was increased after TKR. Possible explanations include changed knee kinematics after a TKR, physical activity level, fall risk, and other unknown factors.

    更新日期:2020-01-04
  • Rib fractures after blunt thoracic trauma in patients with normal versus diminished bone mineral density: a retrospective cohort study
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-11
    J. T. H. Prins, E. M. M. Van Lieshout, M. R. L. Reijnders, M. H. J. Verhofstad, M. M. E. Wijffels

    Abstract This study aimed to evaluate rib fracture rate as well as rib fracture characteristics after thoracic trauma in patients with normal versus diminished bone mineral density (BMD). A retrospective cohort study of persons aged 50 years or older presenting to the Emergency Department after sustaining blunt thoracic trauma between July 1, 2014, and December 31, 2017, was performed. Patient and trauma characteristics and DXA scan results were collected. Rib fracture rate and characteristics were evaluated on a radiograph and/or CT scan of the thorax. In total, 119 patients were included for analysis. Fifty-eight of them (49%) had a diminished BMD. In the remaining 61, the BMD was normal. The diminished BMD group experienced rib fractures more often than the normal BMD group (n = 43 (74%) versus n = 31 (51%); p = 0.014). Patients with diminished BMD suffered low-energy trauma more frequently than the normal BMD group (21 (36%) versus 11 patients (15%), respectively (p = 0.011)). Rib fracture characteristics such as the median number of rib fractures, concomitant intrathoracic injury rate, and rib fracture type distribution were not different between the groups. The rate of rib fractures after blunt thoracic trauma was significantly higher in patients with diminished BMD than in patients with a normal BMD. Differences in number and location of rib fractures between groups could not be proven. When assessing patients aged 50 years or older presenting to the hospital after substantial blunt thoracic trauma, the presence of diminished BMD should be taken into account and the presence of rib fractures should be investigated with appropriate diagnostic procedures. Diminished bone mineral density (i.e., osteopenia or osteoporosis) is associated with increased fracture risk. This study evaluated if diminished BMD increases the rib fracture risk. Patients with diminished BMD have a higher risk of sustaining rib fractures after substantial blunt thoracic trauma, which implicates a lower threshold for CT imaging of the chest.

    更新日期:2020-01-04
  • Education intervention for older adults with osteoporosis: a systematic review
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-11
    Q. Y. Gai, H. Lv, Y. P. Li, Q. M. Fu, P. Li

    Abstract Background Various education interventions were developed for preventing or managing OP, but the effects of those interventions on older adults were inconclusive. Purpose This study evaluated the effectiveness of educational interventions in preventing osteoporosis in older adults. A literature search was performed in MEDLINE (PubMed), Cochrane Library, and CBM (China BioMed Database) from the initial date of each database to Oct 2016. Data Extraction Two investigators independently extracted essential data from qualified studies concerning the settings, population, interventions, follow-ups, and outcomes of interest, namely effects of bone mineral density tests, changes in behavior, knowledge increase, self-efficacy, medication adherence (calcium and vitamin D), and quality of life, respectively. Data Synthesis A total of 17 studies met the inclusion criteria and therefore were included in the current study. The overall quality of the included studies was moderate. We were unable to carry out a meta-analysis due to the heterogeneity of these studies. We fond that compared with control groups, patients’ knowledge of osteoporosis increased significantly (p < .05) through all five interventions, which included PowerPoint presentations and discussion, class-based educational programs, osteoporosis self-management courses, revised health belief model and classes, computerized support programs and brush-up courses. Limitation Studies included in the present study were all conducted in Western countries and only descriptive methods were applied in synthesis due to heterogeneity in interventions and outcomes. Conclusion Education interventions were effective in preventing osteoporosis in older adults. Future research should focus on approaching this issue quantitatively (i.e., through meta-analysis).

    更新日期:2020-01-04
  • Intravenous bisphosphonate therapy in children with spinal muscular atrophy.
    Osteoporos. Int. (IF 3.819) Pub Date : null
    N Nasomyont,L N Hornung,H Wasserman

    This is the first report on safety and efficacy of intravenous bisphosphonates (IV BP) for treatment of disuse osteoporosis and low bone mineral density (BMD) in children with spinal muscular atrophy (SMA). IV BP appears to be safe and effective in fracture rate reduction. However, caution is necessary given the occurrence of an atypical femur fracture. INTRODUCTION Children with SMA are at high risk for fragility fractures and low BMD. IV BP have been used for treatment of disuse osteoporosis in pediatrics. However, safety and efficacy of IV BP in the SMA population has not been reported. METHODS Retrospective chart review of IV BP for treatment of disuse osteoporosis and low BMD in children with SMA at a tertiary pediatric center from 2010 to 2018 RESULTS: Eight patients (50% female; 75% SMA type 1; median age at first infusion 6.7 years) receiving a total of 39 infusions (54% pamidronate, 46% zoledronic acid) were included in this report. Acute phase reactions occurred following 38% and 3% of initial and subsequent infusions, respectively. BMD trended toward improvement at 1 year post-treatment. Among six patients who had > 2 years of follow-up, fracture rate decreased from 1.4 to 0.1 fracture/year. An atypical femur fracture was observed in one patient. CONCLUSION These findings suggest that in children with SMA, IV BP therapy appears to be safe with minimal acute side effects and effective to reduce fracture rate. Caution is still needed given the occurrence of an atypical femur fracture in SMA population.

    更新日期:2019-11-01
  • Secondary prevention of fragility fractures in Asia Pacific: an educational initiative.
    Osteoporos. Int. (IF 3.819) Pub Date : null
    P R Ebeling,D-C Chan,T C Lau,J K Lee,T Songpatanasilp,S H Wong,F L Hew,R Sethi,M Williams

    The Asia -Pacific Bone Academy (APBA) Fracture Liaison Service (FLS) Focus Group educational initiative has stimulated activity across the Asia -Pacific region with the intention of supporting widespread implementation of new FLS. In 2017, the APBA FLS Focus Group developed a suite of tools to support implementation of FLS across the Asia-Pacific region as a component of a multi-faceted educational initiative. This article puts this initiative into context with a narrative review describing the burden of fragility fractures in the region, the current secondary fracture prevention care gap and a summary of emerging best practice. The results of a survey to evaluate the impact of the APBA educational initiative is presented, in addition to commentary on recent activities intended to improve the care of individuals who sustain fragility fractures across the Asia -Pacific. A FLS Toolbox for Asia-Pacific was developed which included the following sections:1. The burden of fragility fractures in the Asia-Pacific region.2. A summary of evidence for FLS in the Asia-Pacific.3. A generic, fully referenced FLS business plan template.4. Potential cost savings accrued by each country, based on a country-specific FLS Benefits Calculator.5. How to start and expand FLS programmes in the Asia-Pacific context.6. A step-by-step guide to setting up FLS in countries in the Asia-Pacific region.7. Other practical tools to support FLS establishment.8. FLS online resources and publications.The FLS Toolbox was provided as a resource to support FLS workshops immediately following the 5th Scientific Meeting of the Asian Federation of Osteoporosis Societies (AFOS) held in Kuala Lumpur in October 2017. The FLS workshops addressed three key themes:• The FLS business case.• Planning the FLS patient pathway.• The role of the FLS coordinator in fragility fracture care management.A follow-up survey of 142 FLS workshop participants was conducted in August-September 2018. The survey included questions regarding how FLS were developed, funded, the scope of service provision and the support provided by the educational initiative. Almost one-third (30.3%) of FLS workshop participants completed the survey. Survey responses were reported for those who had established a FLS at the time the survey was conducted and, separately, for those who had not established a FLS. Findings for those who had established a FLS included:• 78.3% of respondents established a multidisciplinary team to develop the business case for their FLS.• 87.0% of respondents stated that a multidisciplinary team was established to design the patient pathway for their FLS.• 26.1% of respondents stated that their FLS has sustainable funding.• The primary source of funding for FLS was from public hospitals (83.3%) as compared with private hospitals (16.7%).Most hospitals that had not established a FLS at the time the survey was conducted were either in the process of setting-up a FLS (47%) or had plans in place to establish a FLS for which approval is being sought (29%). The primary barrier to establishing a new FLS was lack of sustainable funding. The APBA FLS Focus Group educational initiative has stimulated activity across the Asia-Pacific region with the intention of supporting widespread implementation of new FLS. A second edition of the FLS Toolbox is in development which is intended to complement ongoing efforts throughout the region to expedite widespread implementation of FLS.

    更新日期:2019-11-01
  • Association between a literature-based genetic risk score and bone mineral density of African American women in Women Health Initiative Study.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-02
    X Xiao,Q Wu

    Genetic risk of low BMD in African American women remains unclear. Based on SNPs discovered from a predominantly Caucasian sample, genetic profile was summarized and was found to be significantly associated with BMD variation in African American women. INTRODUCTION Osteoporosis is largely under-recognized and undertreated in African-American women, the post-fracture morbidity and mortality rates in this racial group is rather high. Since BMD was proved to be highly heritable, based on a comprehensive genome-wide meta-analysis that reported 63 BMD-related single nucleotide polymorphisms (SNPs), we aim to unravel the overall genetic risk for decreased BMD and osteoporosis in African-American women. METHODS Genotype data of 842 African American women in a Women's Health Initiative cohort were analyzed. Comprehensive genotype imputation was conducted at the Sanger Imputation Server. Multi-locus genetic risk scores (GRSs) based on 62 BMD-related single-nucleotide polymorphisms (SNPs) were calculated. The association between GRS and BMD was assessed by regression analysis. Longitudinal data was further analyzed using a generalized estimating equation, which helps achieve more efficient and unbiased regression parameters by accounting for the within-subject correlation of responses on dependent variables. RESULTS After adjusting for age, body weight, hormone use, and previous fracture, for every unit increase of GRS.FN and GRS.LS, BMD at hip and lumbar spine decreased 0.124 g/cm2 and 0.086 g/cm2, respectively. Collectively, the model accounted for 34.95% of the femoral neck BMD variation and 25.79% of lumbar spine BMD variation. Notably, GRS.FN and GRS.LS accounted for 2.03% and 2.39% of the total explained variance, respectively. The proportion of BMD variation can be explained by GRSs increasing as participants aged. CONCLUSIONS Genetic risk score was significantly associated with lower BMD in the current study, suggesting that SNPs discovered from prior meta-analysis based on primarily Caucasian population can also explain a considerable proportion of BMD variation in African Americans.

    更新日期:2019-11-01
  • Secondary alterations in bone mineralisation and trabecular thickening occur after long-term estrogen deficiency in ovariectomised rat tibiae, which do not coincide with initial rapid bone loss.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-12-02
    L M O'Sullivan,H Allison,E E Parle,J Schiavi,L M McNamara

    This study delineates the time sequence of changes in bone tissue mineralisation in ovariectomised rats. We report that changes in bone mineral distribution arise secondary to the initial rapid bone loss but coincide with trabecular thickening. We propose that these changes compensate for elevated stresses in remaining trabeculae after bone resorption. INTRODUCTION Recent studies have shown that osteoporosis is not simply a disease of bone loss and microarchitectural degradation but that important changes in tissue composition also occur. Such changes may be a secondary response to early bone loss, but the time sequence of changes in bone mineral distribution is not fully understood. The objective of this study was to quantify the temporal effects of estrogen deficiency on trabecular mineral distribution in the tibia of ovariectomised (OVX) rats. METHODS Weekly in vivo micro-CT scans and morphometric and bone mineral density distribution analyses of the proximal tibia were conducted for the first 4 weeks of estrogen deficiency and then at 8, 14 and 34 weeks. RESULTS Here we report that although trabecular bone volume and architecture are significantly deteriorated within the first 4 weeks of estrogen deficiency, there is no change in the distribution of bone mineral within trabeculae during this initial period. The rate of bone loss in OVX animals dramatically reduced between week 4 and week 14, which coincided with the initiation of increases in trabecular thickness and mineralisation in the OVX group. CONCLUSIONS Together this study reveals for the first time that alterations in bone mineralisation and trabecular thickening arise secondary to the initial rapid bone loss. We propose that these secondary mineralisation changes act to reinforce the trabecular network in an attempt to compensate for the increased loading that ensues after severe bone loss. This study provides an insight into temporal changes in bone mineral distribution in estrogen deficiency.

    更新日期:2019-11-01
  • Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time.
    Osteoporos. Int. (IF 3.819) Pub Date : 2018-10-20
    I T Haider,S M Lobos,N Simonian,T J Schnitzer,W B Edwards

    Computed tomography and finite element modeling were used to assess bone structure at the knee as a function of time after spinal cord injury. Analyzed regions experienced degradation in stiffness, mineral density, and content. Changes were well described as an exponential decay over time, reaching a steady state 3.5 years after injury. INTRODUCTION Spinal cord injury (SCI) is associated with bone fragility and an increased risk of fracture around the knee. The purpose of this study was to investigate bone stiffness and mineral content at the distal femur and proximal tibia, using finite element (FE) and computed tomography (CT) measures. A cross-sectional design was used to compare differences between non-ambulatory individuals with SCI as a function of time after injury (0-50 years). METHODS CT scans of the knee were obtained from 101 individuals who experienced an SCI 30 days to 50 years prior to participation. Subject-specific FE models were used to estimate stiffness under axial compression and torsional loading, and CT data was analyzed to assess volumetric bone mineral density (vBMD) and bone mineral content (BMC) for integral, cortical, and trabecular compartments of the epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. RESULTS Bone degradation was well described as an exponential decay over time (R2 = 0.33-0.83), reaching steady-state levels within 3.6 years of SCI. Individuals at a steady state had 40 to 85% lower FE-derived bone stiffness and robust decreases in CT mineral measures, compared to individuals who were recently injured (t ≤ 47 days). Temporal and spatial patterns of bone loss were similar between the distal femur and proximal tibia. CONCLUSIONS After SCI, individuals experienced rapid and profound reductions in bone stiffness and bone mineral at the knee. FE models predicted similar reductions to axial and torsional stiffness, suggesting that both failure modes may be clinically relevant. Importantly, CT-derived measures of bone mineral alone underpredicted the impacts of SCI, compared to FE-derived measures of stiffness. TRIAL REGISTRATION ClinicalTrials.gov (NCT01225055, NCT02325414).

    更新日期:2019-11-01
  • Gene-based GWAS analysis for consecutive studies of GEFOS.
    Osteoporos. Int. (IF 3.819) Pub Date : 2018-10-12
    W Zhu,C Xu,J-G Zhang,H He,K-H Wu,L Zhang,Y Zeng,Y Zhou,K-J Su,H-W Deng

    By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal metabolism. INTRODUCTION Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes. METHODS BMD-associated genes were identified by combining the summary statistic P values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the P values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples. RESULTS Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (UBTF, AAAS, and C11orf58) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants. CONCLUSIONS Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.

    更新日期:2019-11-01
  • Impact of prescription drugs on second fragility fractures among US Medicare patients.
    Osteoporos. Int. (IF 3.819) Pub Date : 2018-09-21
    J C Munson,J P W Bynum,J-E Bell,C McDonough,Q Wang,T Tosteson,A N A Tosteson

    Drugs that increase the risk of fracture are commonly prescribed to survivors of a fragility fracture. This study shows that starting new high-risk medications after fracture increases the risk of a second, potentially preventable fracture. For most drug classes, however, it is safe to continue medications taken before the fracture. INTRODUCTION Most patients who survive a fragility fracture are subsequently exposed to prescription drugs that have been linked to increased fracture risk. This study was designed to quantify the extent to which current prescribing practices result in potentially preventable second fractures. METHODS We analyzed a cohort of 138,526 Medicare beneficiaries who returned to the community after a fragility fracture. Post-fracture drug use was defined using retail pharmacy fills. The risk of second fracture associated with individual drug classes was analyzed using Cox proportional hazard models. Data were further analyzed to determine whether there is a difference in risk between continuing previous therapy and initiating new therapy after fracture. RESULTS Many drug classes previously identified as increasing fracture risk were not associated with increased fracture risk in this cohort. Discontinuing therapy at the time of fracture was only beneficial for patients taking selective serotonin reuptake inhibitors; however, initiating therapy in previous non-users increased second fracture risk for five classes of drugs (selective serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, proton pump inhibitors, and non-benzodiazepine hypnotics). CONCLUSION Discontinuing high-risk drugs after fracture was not generally protective against subsequent fractures. Preventing the addition of new medications may result in greater improvements in post-fracture care.

    更新日期:2019-11-01
  • Notch in skeletal physiology and disease.
    Osteoporos. Int. (IF 3.819) Pub Date : 2018-09-09
    E Canalis

    Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling. The effects of Notch are cell-context dependent, and the four Notch receptors carry out specific functions in the skeleton. Gain- and loss-of-function mutations of components of the Notch signaling pathway result in a variety of congenital disorders with significant craniofacial and skeletal manifestations. The Notch ligand Jag1 is a determinant of bone mineral density, and Notch plays a role in the early phases of fracture healing. Alterations in Notch signaling are associated with osteosarcoma and with the metastatic potential of carcinoma of the breast and of the prostate. Controlling Notch signaling could prove useful in diseases of Notch gain-of-function and in selected skeletal disorders. However, clinical data on agents that modify Notch signaling are not available. In conclusion, Notch signaling is a novel pathway that regulates skeletal homeostasis in health and disease.

    更新日期:2019-11-01
  • Low free T3 to free T4 ratio was associated with low muscle mass and impaired physical performance in community-dwelling aged population.
    Osteoporos. Int. (IF 3.819) Pub Date : null
    S H Kong,J H Kim,Y J Park,J H Lee,A R Hong,C S Shin,N H Cho

    In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance. PURPOSE We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort. METHODS We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht2) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB). RESULTS Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht2, stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates. CONCLUSION Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.

    更新日期:2019-11-01
  • Optimizing HR-pQCT workflow: a comparison of bias and precision error for quantitative bone analysis.
    Osteoporos. Int. (IF 3.819) Pub Date : null
    D E Whittier,A N Mudryk,I D Vandergaag,L A Burt,S K Boyd

    Manual correction of automatically generated contours for high-resolution peripheral quantitative computed tomography can be time consuming and introduces precision error. However, bias related to the automated protocol is unknown. This study provides insight into error bias that is present when using uncorrected contours and inter-operator precision error based on operator training. INTRODUCTION High-resolution peripheral quantitative computed tomography workflow includes manually correcting contours generated by the manufacturer's automated protocol. There is interest in minimizing corrections to save time and reduce precision error; however, bias related to the automated protocol is unknown. This study quantifies error bias when contours are uncorrected and identifies the impact of operator training on bias and precision error. METHODS Forty-five radii and tibiae scans across a representative range of bone density were analyzed using the automated and manually corrected contours of three operators, with training ranging from beginner to expert, and compared with a "ground truth" to estimate bias. Inter-operator precision was measured across operators. RESULTS The tibia had greater error bias than the radius when contours were uncorrected, with compartmental bone mineral densities and cortical microarchitecture having greatest biases, which could have significant implications for interpretation of studies using this skeletal site. Bias and precision error were greatest when contours were corrected by the beginner operator; however, when this operator was removed, bias was no longer present and inter-operator precision was between 0.01 and 3.74% for all parameters except cortical porosity. CONCLUSION These findings establish the need for manual correction and provide guidance on operator training needed to maximize workflow efficiency.

    更新日期:2019-11-01
  • Relationship between bone mineral content and bone turnover markers, sex hormones and calciotropic hormones in pre- and early pubertal children.
    Osteoporos. Int. (IF 3.819) Pub Date : null
    S J Zürcher,N Borter,M Kränzlin,P Neyer,U Meyer,R Rizzoli,S Kriemler

    We investigated associations between bone mineral content (BMC) and bone-related biomarkers (BM) in pre-and early pubertal children of both sexes. In this population, we found that bone turnover markers explain a small part of BMC variance. INTRODUCTION It is still debated whether BM including bone turnover markers (BTM), sex hormones and calciotropic (including cortisol) hormones provide information on BMC changes during growth. METHODS Three hundred fifty-seven girls and boys aged 6 to 13 years were included in this study. BM was measured at baseline and BMC twice at 9 months and 4 years using DXA. Relationship between BMs was assessed using principal component analysis (PCA). BM was tested in its ability to explain BMC variation by using structural equation modelling (SEM) on cross-sectional data. Longitudinal data were used to further assess the association between BM and BMC variables. RESULTS BMC and all BMs, except calciotropic hormones, increased with age. PCA in BM revealed a three-factor solution (BTM, sex hormones and calciotropic hormones). In the SEM, age accounted for 61% and BTM for 1.2% of variance in BMC (cross-sectional). Neither sex nor calciotropic hormones were BMC explanatory variables. In the longitudinal models (with single BM as explanatory variables), BMC, age and sex at baseline accounted for 79-81% and 70-75% in BMC variance at 9 months and 4 years later, respectively. P1NP was consistently associated with BMC. CONCLUSION BMC strongly tracks in pre- and early pubertal children. In this study, only a small part of BMC variance was explained by single BTM at the beginning of pubertal growth.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Bisphosphonate drug holidays.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-10-17
    S Nayak,S L Greenspan

    更新日期:2019-11-01
  • Drug holidays in osteoporosis treatment: mind the gaps!
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-10-17
    P Anagnostis,I Lambrinoudaki,E Kenanidis,M Potoupnis,E Tsiridis,D G Goulis

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Atypical femur fracture incidence in women increases with duration of bisphosphonate exposure.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-09-27
    J C Lo,C D Grimsrud,S M Ott,M Chandra,R L Hui,B Ettinger

    In a northern California population of older women who were treated with oral bisphosphonate drugs, the incidence of atypical femur fracture, a rare complication of treatment, increased with longer duration of bisphosphonate exposure. These findings align with those previously reported in an independent southern California population. INTRODUCTION The age-adjusted incidence of atypical femur fracture (AFF) reported in southern California increased with bisphosphonate (BP) exposure, ranging up to 113 per 100,000 person-years for 8-10-year exposure. This study examines the incidence of AFF in a northern California population. METHODS Women age 45-89 years who initiated oral BP during 2002-2014 in Kaiser Permanente Northern California were followed for AFF outcome, defined by a primarily transverse diaphyseal femur fracture through both cortices, with focal periosteal/endosteal hypertrophy, minimal trauma, and minimal/no comminution. Total BP exposure was determined from dispensed prescriptions. The incidence of AFF, calculated for 2-year BP categories ranging from < 2 to > 10 years, was age-adjusted using the 2000 US Census. RESULTS Among 94,542 women, 107 experienced an AFF during or < 1 year after BP cessation (mean exposure 6.6 ± 3.0 years and total days' supply 5.7 ± 2.8 years at AFF). A strong relationship between AFF incidence and increasing BP exposure was seen, more than doubling for each 2-year category until 8-10 years. Among women with 2- to < 4-year BP, the crude and age-adjusted incidence was 18 and 9 per 100,000 person-years but increased over 2- and 5-fold for women with 4- to < 6- and 6- to < 8-year BP, respectively. For those receiving ≥ 8-year BP, the crude and age-adjusted incidence peaked at 196 and 112 per 100,000 person-years exposure. CONCLUSION Incidence of AFF increases markedly after 4-6 years of BP. These trends align with southern California and confirm a strong BP duration-related risk of this rare but serious event.

    更新日期:2019-11-01
  • The association between sarcopenia and osteoporotic vertebral compression refractures.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-09-05
    W-F Wang,C-W Lin,C-N Xie,H-T Liu,M-Y Zhu,K-L Huang,H-L Teng

    Sarcopenia was reported to be significantly associated with osteoporosis. In this study, we reported for the first time that sarcopenia was an independent risk predictor of osteoporotic vertebral compression refractures (OVCRFs). Other risk factors of OVCRFs are low bone mass density T-scores, female sex, and advanced age. INTRODUCTION The purpose of this study was to investigate the association between osteoporotic vertebral compression refractures (OVCRFs) and sarcopenia, and to identify other risk factors of OVCRFs. METHODS We evaluated 237 patients with osteoporotic vertebral compression fracture who underwent percutaneous kyphoplasty (PKP) in our hospital from August 2016 to December 2017. To diagnose sarcopenia, a cross-sectional computed tomography (CT) image at the inferior aspect of the third lumbar vertebra (L3) was selected for estimating muscle mass. Grip strength was used to assess muscle strength. Possible risk factors, such as age, sex, body mass index (BMI), bone mineral density (BMD), location of the treated vertebra, anterior-posterior ratio (AP ratio) of the fractured vertebra, cement leakage, and vacuum clefts, were assessed. The multivariable analysis was used to determine the risk factors of OVCRFs. RESULTS During the follow-up period, OVCRFs occurred in 64 (27.0%) patients. Sarcopenia was present in 48 patients (20.3%), including 21 OVCRFs and 27 non-OVCRFs patients. Sarcopenia was significantly correlated with advanced age, lower BMI, lower BMD, and hypoalbuminemia. Compared with non-sarcopenic patients, sarcopenic patients had higher OVCRFs risk. In univariate analysis, sarcopenia (p = 0.003), female (p = 0.024), advanced age (≥ 75 years; p < 0.001), lower BMD (p < 0.001), lower BMI (p = 0.01), TL junction (vertebral levels at the thoracolumbar junction) (p = 0.01), cardiopulmonary comorbidity (p = 0.042), and hypoalbuminemia (p = 0.003) were associated with OVCRFs. Multivariable analysis revealed that sarcopenia (OR 2.271; 95% CI 1.069-4.824, p = 0.033), lower BMD (OR 1.968; 95% CI 1.350-2.868, p < 0.001), advanced age (≥ 75 years; OR 2.431; 95% CI 1.246-4.744, p = 0.009), and female sex (OR 4.666; 95% CI 1.400-15.552, p = 0.012) were independent risk predictors of OVCRFs. CONCLUSIONS Sarcopenia is an independent risk predictor of osteoporotic vertebral compression refractures. Other factors affecting OVCRFs are low BMD T-scores, female sex, and advanced age.

    更新日期:2019-11-01
  • Elderly males with or without existing osteoporotic vertebral fracture have much lower future vertebral fracture risk than elderly females: the MrOS (Hong Kong) year-4 follow-up spine radiograph study.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-09-04
    Y X J Wáng,N Che-Nordin,M Deng,J F Griffith,J C S Leung,A W L Kwok,P C Leung,T C Y Kwok

    MrOS (Hong Kong)'s year-4 follow-up shows, for subjects at baseline without vertebral deformity (VD) and endplate or/and cortex fracture (ECF), the VD progression/new VD rate during follow-up in males was half of our paired MsOS (Hong Kong) study's results. For those with VD or ECF, the VD progression/new VD was less than one sixth of females' rate. INTRODUCTION This study documents MrOS (Hong Kong)'s year-4 follow-up, and the results are compared with the MsOS (Hong Kong) study. Of elderly females with Genant's grade-0, -1, -2, and -3 VD, at year-4 follow-up, 4.6%, 8%, 10.6%, and 28.9% had at least one VD progression or incident VD, respectively. METHODS Spine radiographs of 1500 Chinese males with baseline (mean age 71.7 years, range 65-91 years) and year-4 follow-up were evaluated according to Genant's VD criteria and ECF (non-existent, ECF0; or existent, ECF1). Grade-2 VDs were divided into mild (VD2m, 25-34% height loss) and severe (VD2s, 34-40% height loss) subgroups. Study subjects were graded into eight categories: VD0/ECF0, VD1/ECF0, VD2m/ECF0, VD0/ECF1, VD1/ECF1, VD2m/ECF1, VD2s/ECF1, and VD3/ECF1. With an existing VD, a further height loss of ≥ 15% was a VD progression. A new VD incident was a change from grade-0 to grade-2/3, or to grade-1 with ≥ 10% height loss. RESULTS Of subjects with Genant's grade-0, 2.05% (25/1219) developed at least one VD progression or/and new VD, while of subjects with Genant's grade-1, -2, and -3 VD, only 2% (3/149), 3.1% (3/96), and 2.8% (1/36) developed at least one VD progression/new VD, respectively. Among the three ECF0 groups, there was a significant difference in new ECF incidence, with VD0/ECF0 being the lowest and VD2m/ECF0 being the highest. CONCLUSION VD progression/new VD is much less common in elderly men than in elderly women. Vertebrae with VD had a higher risk of developing ECF.

    更新日期:2019-11-01
  • A bone resorption marker as predictor of rate of change in femoral neck size and strength during the menopause transition.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-09-02
    A Shieh,S Ishii,G A Greendale,J A Cauley,C Karvonen-Gutierrez,A S Karlamangla

    We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength. PURPOSE Composite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT. METHODS We used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women. RESULTS Adjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample. CONCLUSIONS Measuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.

    更新日期:2019-11-01
  • Lessons learned with Bone Health TeleECHO: making treatment decisions when guidelines conflict.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-09-01
    M S Rothman,T P Olenginski,I Stanciu,K Krohn,E M Lewiecki

    Clinical practice guidelines provide helpful information for managing patients with metabolic bone disease. Good guidelines are based on the best available medical evidence; however, guidelines from different societies can conflict. Additionally, it is not possible for a guideline to anticipate the vast variability of circumstances, comorbidities, previous medical experiences, cultural differences, and preferences in real-world patients. Bone Health TeleECHO is a strategy for sharing knowledge on the care of patients with skeletal diseases through ongoing interactive videoconferences. We report three cases based on those presented at Bone Health TeleECHO, where, through discussion, treatment outside of commonly used guidelines was ultimately recommended. Guidelines developed by different organizations may provide "evidence-based" or "informed" recommendations which do not account for the variability of clinical circumstances encountered in the care of individual patients. This highlights the importance of Bone Health TeleECHO, where healthcare professionals can share knowledge, individualize treatment decisions, and improve patient care.Learning objectives At the end of this activity participants should be able to:• Distinguish between the onset and off of bisphosphonates versus other medications used in the prevention and treatment of osteoporosis and how this affects choice of a "drug holiday."• Understand the limitations of clinical practices guidelines in the care of an individual patient and how interactive video conferencing can assist with decision making.• Recognize that patients treated with glucocorticoids at high risk for fracture can benefit from more aggressive interventions for osteoporosis.

    更新日期:2019-11-01
  • Rate of drop in serum calcium as a predictor of hypocalcemic symptoms post total thyroidectomy.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-30
    R K Saad,N G Boueiz,V C Akiki,G A E-H Fuleihan

    The rate of drop in serum calcium post total thyroidectomy is a predictor of hypocalcemic symptoms in adults, after adjusting for other significant covariates. INTRODUCTION Test the hypothesis that rate of drop in calcium is a significant and independent predictor of post-operative hypocalcemic symptoms post total thyroidectomy. METHODS A retrospective chart review (electronic and hard copy) for 429 patients who underwent total thyroidectomy from January 2011 to December 2016. We collected information on demographics, clinical characteristics, information on surgical intervention, histopathology reports, clinical course, biochemistries, treatments and discharge instructions. RESULTS Sixty-one patients (14%) developed post-operative hypocalcemic symptoms. The rate of calcium drop, younger age, female gender, and lower body mass index, and the presence of parathyroid tissue in resected specimen all correlated significantly with the development of symptoms. The rate of drop in serum calcium and the post-operative serum calcium level remained the only significant predictors of symptom development, after adjustment for other significant co-variates. Using a receiver operating characteristics curve, a cutoff rate of calcium drop > 0.083 mg/dl/h, that is 1 mg/dl over 12 h, has a sensitivity of 71% and specificity of 73% for detecting hypocalcemic symptoms. CONCLUSION The rate of drop of serum calcium post total thyroidectomy significantly and independently correlated with the development of hypocalcemic symptoms. Patients with a rate of drop < 1 mg/dl/12 h may be considered for earlier discharge and less aggressive management peri-operatively.

    更新日期:2019-11-01
  • A study of dynamic contrast-enhanced MR imaging features and influence factors of pelvic bone marrow in adult females.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-28
    X Zhang,H Pang,Y Dong,D Shi,F Liu,Y Luo,T Yu,X Wang

    Perfusion of the pelvic bone marrow is reduced in the postmenopausal group and with age. Quantitative dynamic contrast-enhanced MRI could reflect the blood supply characteristics and hemodynamic changes of the pelvic bone marrow. These results contribute to the description of osteoporosis in the postmenopausal females and the elderly. INTRODUCTION To investigate the effect of menstrual status and age on the perfusion of pelvic bone marrow in adult females using quantitative dynamic contrast-enhanced MRI (DCE-MRI). METHODS In total, 96 adult females who underwent DCE-MRI between September 2017 and December 2017 were included. All the subjects' quantitative DCE-MRI parameters of pelvic bone marrow were measured and retrospectively analyzed, including Ktrans (volume transfer constant), Kep (efflux rate constant), and Ve (interstitial volume). According to their menstrual status, the subjects were divided into a premenopausal group (n = 39) and a postmenopausal group (n = 57), and the two groups were then divided into four subgroups according to age. The intraobserver reliability was assessed by the intraclass correlation coefficient (ICC). The parameters were compared between different menstrual status groups and age subgroups by Mann-Whitney test, and Spearman correlation analysis was used to evaluate the correlation between the age and the quantitative parameters. RESULTS The ICCs of the Ktrans, Kep, and Ve values were 0.989, 0.974, and 0.920, respectively. Ktrans, Kep, and Ve of the premenopausal group were significantly higher than those of the postmenopausal group (P < 0.05). The overall age was negatively correlated with Ktrans, Kep, and Ve (r = - 0.590, - 0.357, and - 0.381, respectively, P < 0.05). In the premenopausal group, Ktrans and Ve were significantly higher in subgroup 1 (≤ 40 years) compared with subgroup 2 (> 40 years) (P < 0.05), and age showed a negative correlation with Ktrans and Ve (r = - 0.344 and - 0.334, respectively, P < 0.05). In the postmenopausal group, Ktrans and Kep were significantly higher in subgroup 3 (≤ 60 years) compared with subgroup 4 (> 60 years) (P < 0.05), and age showed a negative correlation with Ktrans and Kep (r = - 0.460 and - 0.303, respectively, P < 0.05). CONCLUSION Menstrual status and age have significant effects on the perfusion of the pelvic bone marrow microenvironment in adult females and that the microenvironment of the pelvic bone marrow displays different changes at different age stages. Quantitative DCE-MRI has contributed to the interpretation of the pelvic bone marrow perfusion status.

    更新日期:2019-11-01
  • Comorbidity as the dominant predictor of mortality after hip fracture surgeries.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-28
    Eric Wei Liang Cher,John Carson Allen,Tet Sen Howe,Joyce Suang Bee Koh

    The aim of this study was to investigate the association of surgical delay and comorbidities with the risk of mortality after hip fracture surgeries. We found that CCI was the dominant factor in predicting both short- and long-term mortality, and its effect is vital in the prognostication of survivorship. INTRODUCTION Hip fracture is a growing concern and a delay in surgery is often associated with a poorer outcome. We hypothesized that a higher Charlson Comorbidity Index (CCI) portends greater risk of mortality than a delay in surgery. Our aim was to investigate the associations of surgical delay and CCI with risk of mortality and to determine the dominant predictor. METHODS This retrospective study examines hip fracture data from a large tertiary hospital in Singapore over the period January 2013 through December 2015. Data collected included age, gender, CCI, delay of surgery, fracture patterns, and the American Society of Anaesthesiologist (ASA) score. Post-operative outcomes analyzed included mortality at inpatient, at 30 and 90 days, and at 2 years. RESULTS A total of 1004 patients with hip fractures were included in this study. Study mortality rates were 1.1% (n = 11) during in-hospital admission, 1.8% (n = 18) at 30 days, 2.7% (n = 27) at 90 days, and 13.3% (n = 129) at 2 years. Lost to follow-up rate at 2 years was 3.3%. We found that CCI was consistently the dominant factor in predicting both short- and long-term mortality. A CCI score of 5 was identified as the inflection point above which comorbidity at baseline presented a greater risk of mortality than a delay in surgery. CONCLUSION Our analysis showed that CCI is the dominant predictor of both short- and long-term mortality compared with delay in surgery. The effect of CCI is vital in the prognostication of mortality in patients surgically treated for hip fractures.

    更新日期:2019-11-01
  • Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP-a systematic review.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-26
    F D Højsager,M S Rand,S B Pedersen,N Nissen,N R Jørgensen

    To assess the time from fracture until bone turnover markers (BTM), which are biochemical markers reflecting in vivo bone formation and resorptive activity, have returned to a stable level since BTM have been shown to be at least as good as bone mineral density in monitoring the effect of anti-resorptive treatment in osteoporosis. This study searched for articles in PUBMED, CINAHL, Medline, EM-BASE, and Cochrane, and identified 3486 unique articles. These articles were screened based on predefined inclusion and exclusion criteria. Seven articles addressing time to normalization of either CTX, PINP, osteocalcin, or bone-specific alkaline phosphatase after a recent fracture were identified and these were analyzed qualitatively. CTX appeared to return to baseline within 6 months. PINP appeared to return to baseline within 6 months and interestingly dip below baseline after a year. Osteocalcin was elevated throughout the first year after a fracture, with most changes in the first 6 months. Bone-specific alkaline phosphatase (BAP) was increased for up to a year, however with a discrepancy between used assays. Seven studies were identified, showing CTX and PINP to return to baseline within 6 months. OC was elevated for 12 months. BAP was increased for up to a year. However, none of these studies had fasting patients and a long follow-up period with regular measurements. The studies could indicate that the BTM CTX and PINP have returned to baseline within 6 months; however, further studies are needed assessing pre-analytical factors while having a long follow-up. Bone turnover markers appear as good as or better than bone mineral density in monitoring the effect of anti-resorptive medication in osteoporosis. This study tries to identify the time from fracture until BTM are back at baseline. Most studies did not however take pre-analytical variation into consideration. Further research is therefore needed.

    更新日期:2019-11-01
  • Bone health in estrogen-free contraception.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-26
    P Hadji,E Colli,P-A Regidor

    Estrogens and progestogens influence the bone. The major physiological effect of estrogen is the inhibition of bone resorption whereas progestogens exert activity through binding to specific progesterone receptors. New estrogen-free contraceptive and its possible implication on bone turnover are discussed in this review. Insufficient bone acquisition during development and/or accelerated bone loss after attainment of peak bone mass (PBM) are 2 processes that may predispose to fragility fractures in later life. The relative importance of bone acquisition during growth versus bone loss during adulthood for fracture risk has been explored by examining the variability of areal bone mineral density (BMD) (aBMD) values in relation to age. Bone mass acquired at the end of the growth period appears to be more important than bone loss occurring during adult life. The major physiological effect of estrogen is the inhibition of bone resorption. When estrogen transcription possesses binds to the receptors, various genes are activated, and a variety modified. Interleukin 6 (IL-6) stimulates bone resorption, and estrogen blocks osteoblast synthesis of IL-6. Estrogen may also antagonize the IL-6 receptors. Additionally, estrogen inhibits bone resorption by inducing small but cumulative changes in multiple estrogen-dependent regulatory factors including TNF-α and the OPG/RANKL/RANK system. Review on existing data including information about new estrogen-free contraceptives. All progestins exert activity through binding to specific progesterone receptors; hereby, three different groups of progestins exist: pregnanes, gonanes, and estranges. Progestins also comprise specific glucocorticoid, androgen, or mineralocorticoid receptor interactions. Anabolic action of a progestogen may be affected via androgenic, anti-androgenic, or synadrogenic activity. The C 19 nortestosterone class of progestogens is known to bind with more affinity to androgen receptors than the C21 progestins. This article reviews the effect of estrogens and progestogens on bone and presents new data of the currently approved drospirenone-only pill. The use of progestin-only contraceptives leading to an estradiol level between 30 and 50 pg/ml does not seem to lead to an accelerate bone loss.

    更新日期:2019-11-01
  • Rapid suppression of bone formation marker in response to sleep restriction and circadian disruption in men.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-26
    C M Swanson,W M Kohrt,P Wolfe,K P Wright,S A Shea,S W Cain,M Munch,N Vujović,C A Czeisler,E S Orwoll,O M Buxton

    We describe the time course of bone formation marker (P1NP) decline in men exposed to ~ 3 weeks of sleep restriction with concurrent circadian disruption. P1NP declined within 10 days and remained lower with ongoing exposure. These data suggest even brief exposure to sleep and circadian disruptions may disrupt bone metabolism. INTRODUCTION A serum bone formation marker (procollagen type 1 N-terminal, P1NP) was lower after ~ 3 weeks of sleep restriction combined with circadian disruption. We now describe the time course of decline. METHODS The ~ 3-week protocol included two segments: "baseline," ≥ 10-h sleep opportunity/day × 5 days; "forced desynchrony" (FD), recurring 28 h day (circadian disruption) with sleep restriction (~ 5.6-h sleep per 24 h). Fasted plasma P1NP was measured throughout the protocol in nine men (20-59 years old). We tested the hypothesis that PINP would steadily decline across the FD intervention because the magnitude of sleep loss and circadian misalignment accrued as the protocol progressed. A piecewise linear regression model was used to estimate the slope (β) as ΔP1NP per 24 h with a change point mid-protocol to estimate the initial vs. prolonged effects of FD exposure. RESULTS Plasma P1NP levels declined significantly within the first 10 days of FD ([Formula: see text] = - 1.33 μg/L per 24 h, p < 0.0001) and remained lower than baseline with prolonged exposure out to 3 weeks ([Formula: see text] = - 0.18 μg/L per 24 h, p = 0.67). As previously reported, levels of a bone resorption marker (C-telopeptide (CTX)) were unchanged. CONCLUSION Sleep restriction with concurrent circadian disruption induced a relatively rapid decline in P1NP (despite no change in CTX) and levels remained lower with ongoing exposure. These data suggest (1) even brief sleep restriction and circadian disruption can adversely affect bone metabolism, and (2) there is no P1NP recovery with ongoing exposure that, taken together, could lead to lower bone density over time.

    更新日期:2019-11-01
  • The association between type 2 diabetes mellitus, hip fracture, and post-hip fracture mortality: a multi-state cohort analysis.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-25
    C Tebé,D Martínez-Laguna,C Carbonell-Abella,C Reyes,V Moreno,A Diez-Perez,G S Collins,D Prieto-Alhambra

    Type 2 diabetes mellitus (T2DM) is associated with an excess risk of fractures and overall mortality. This study compared hip fracture and post-hip fracture mortality in T2DM and non-diabetic subjects. The salient findings are that subjects in T2DM are at higher risk of dying after suffering a hip fracture. INTRODUCTION Previous research suggests that individuals with T2DM are at an excess risk of both fractures and overall mortality, but their combined effect is unknown. Using multi-state cohort analyses, we estimate the association between T2DM and the transition to hip fracture, post-hip fracture mortality, and hip fracture-free all-cause death. METHODS Population-based cohort from Catalonia, Spain, including all individuals aged 65 to 80 years with a recorded diagnosis of T2DM on 1 January 2006; and non-T2DM matched (up to 2:1) by year of birth, gender, and primary care practice. RESULTS A total of 44,802 T2DM and 81,233 matched controls (53% women, mean age 72 years old) were followed for a median of 8 years: 23,818 died without fracturing and 3317 broke a hip, of whom 838 subsequently died. Adjusted HRs for hip fracture-free mortality were 1.32 (95% CI 1.28 to 1.37) for men and 1.72 (95% CI 1.65 to 1.79) for women. HRs for hip fracture were 1.24 (95% CI 1.08 to 1.43) and 1.48 (95% CI 1.36 to 1.60), whilst HRs for post-hip fracture mortality were 1.28 (95% CI 1.02 to 1.60) and 1.57 (95% CI 1.31 to 1.88) in men and women, respectively. CONCLUSION T2DM individuals are at increased risk of hip fracture, post-hip fracture mortality, and hip fracture-free death. After adjustment, T2DM men were at a 28% higher risk of dying after suffering a hip fracture and women had 57% excess risk of post-hip fracture mortality.

    更新日期:2019-11-01
  • Natural history of incomplete atypical femoral fractures in patients after a prolonged and variable course of bisphosphonate therapy-a long-term radiological follow-up.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-23
    M A Png,P C Mohan,J S B Koh,C Y Howe,T S Howe

    Understanding the natural history of lateral femoral stress fractures helps to guide their management. Improvement in their radiographic characteristics is rare. Progression was generally sequential, most developing an incomplete fracture line before fracture displacement. Stopping bisphosphonates decreased the fracture rate, a feasible management option for lesions without incomplete fracture lines. INTRODUCTION Retrospective study evaluating the natural history of lateral femoral stress fractures (FSF) by serial radiography over a variable period of time in a cohort of patients treated for some time with bisphosphonates for osteoporosis, whilst also identifying the fracture response in cases where bisphosphonates were discontinued. METHODS The radiographs of 76 consecutive patients (92 femurs) with 161 FSF were reviewed to document their change over time. Femurs were classified into the following: A-normal, B-focal cortical thickening, C-dreaded black line and D-displaced fracture. Bisphosphonate history was recorded. RESULTS 66.5% FSF showed group stability between the first and last radiographs: group B (79.1%), group C (45.7%). 28.6% progressed, mostly following an ordered sequence starting from group A, progressing to B, then C, before culminating in D. Progression rate was as follows: A-100% (11/11), B-18.3% (21/115), C-40% (14/35). Regression in FSF was uncommon-5.6% (8/161). 34.8% (32/92) sustained displaced fractures. Kaplan-Meier analysis showed statistically significant difference between the groups; median survival (95% CI): A-4189 (-), B-3383.0 (-), C-1807 (0.0-3788.6) and progression to displaced fracture when bisphosphonate had been stopped for at least 6 months. The group without recent bisphosphonates had a lower group progression rate (17.1%, 12/70). Nevertheless, 10.9% (5/46) progressed to displaced fracture. This group also had the highest proportion of stable (77.1%, 54/70) and regressive lesions (5.7%, 4/70). CONCLUSIONS In FSF, there is natural progression from normal bone, to focal cortical thickening, to dreaded black line and eventually to displaced fracture. Most lesions persist, remaining static or progressing, especially if a dreaded black line is present and bisphosphonates are continued. Regression is uncommon and more frequent when bisphosphonates are discontinued. Despite stopping bisphosphonates, there remains a 10.9% risk of progression to displaced fracture.

    更新日期:2019-11-01
  • Percutaneous vertebroplasty versus non-operative treatment for osteoporotic vertebral compression fractures: a meta-analysis of randomized controlled trials.
    Osteoporos. Int. (IF 3.819) Pub Date : 2019-08-04
    S Lou,X Shi,X Zhang,H Lyu,Z Li,Y Wang

    PURPOSE Osteoporotic vertebral compression fractures (OVCFs) are common in the elderly population and are often treated using percutaneous vertebroplasty (PVP). However, the effectiveness of PVP reported by various randomized controlled trials (RCTs) is inconclusive. This study aimed to analyze, from published literature, the efficacy and safety of PVP for OVCFs. METHODS A search was conducted in Medline, EMBASE, and Cochrane Libraries since their respective inception on January 1, 2019, for RCTs of OVCFs treated with PVP compared with non-operative treatment. The primary outcomes were pain relief at 1 to 2 weeks, 1 to 3 months, and 6 to 12 months. The secondary outcome was the rate of occurrence of new vertebral fractures. Meta-analysis was performed using a random effect model. RESULTS A total of 13 RCTs comprising 1624 patients were included. For the blinded studies, statistical differences were found between PVP and the sham injection group for the 3 primary outcomes in the subgroup of the Vertebroplasty for Acute Painful Osteoporotic fractURes (VAPOUR) trial. Although pain scores were similar between the PVP group and the sham injection group for the VAPOUR trial at each period, the effect size of PVP increased over time. For the open-label studies, PVP significantly reduced pain at all time points. The risk of new vertebral fractures was similar between the PVP groups and control groups. CONCLUSIONS Application of PVP was effective and safe only in patients with acute OVCFs having persistent and severe pain. No benefits were recorded, among patients with older fractures or those bearing non-severe symptoms.

    更新日期:2019-11-01
  • Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates.
    Osteoporos. Int. (IF 3.819) Pub Date : null
    P D Miller,N Pannacciulli,J Malouf-Sierra,A Singer,E Czerwiński,H G Bone,C Wang,S Huang,A Chines,W Lems,J P Brown

    Transitioning postmenopausal women with osteoporosis from a bisphosphonate to denosumab appears to be safe and more effective at improving BMD than continuing treatment with a bisphosphonate. INTRODUCTION We conducted a patient-level pooled analysis of four studies to estimate the efficacy and safety of transitioning to denosumab vs. continuing bisphosphonate treatment in postmenopausal women who previously received oral bisphosphonates. METHODS Patients received 60 mg denosumab once every 6 months or a bisphosphonate (oral alendronate, risedronate, ibandronate, or intravenous zoledronic acid). Endpoints were change from baseline in lumbar spine, total hip, femoral neck, and 1/3 radius BMD at month 12, change from baseline in serum CTX-1 and P1NP, and incidence of adverse events. RESULTS A total of 2850 randomized patients (1424 bisphosphonate:1426 denosumab) were included in the analysis. Percentage change in BMD was significantly greater (p < 0.001) for denosumab vs. bisphosphonate at each skeletal site; differences in BMD changes ranged from 0.6 to 2.0%. Percentage decrease in serum CTX-1 and P1NP was significantly greater (p < 0.0001) for denosumab vs. bisphosphonate at months 1, 6, and 12; in the denosumab group only, percentage change in serum CTX-1 at month 1 was significantly correlated with percentage change in lumbar spine and total hip BMD at month 12. The incidences of adverse events were similar between treatment groups. Three patients (one bisphosphonate and two denosumab) had atypical femoral fractures, all from the denosumab vs. zoledronic acid study. CONCLUSION Postmenopausal women can safely transition from a bisphosphonate to denosumab, which is more effective at improving BMD than continuing with a bisphosphonate. CLINICAL TRIALS REGISTRATION NCT00377819, NCT00919711, NCT00936897, NCT01732770.

    更新日期:2019-11-01
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