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“Pregnancy and Lactation Associated Osteoporosis”

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Abstract

Pregnancy-associated osteoporosis (PAO) is a rare condition of skeletal fragility affecting women in pregnancy or the postpartum period. During normal pregnancy and lactation, substantial changes in calcium metabolism and skeletal physiology occur in order to meet the demands of the developing foetus. Whilst these adaptations are reversible and generally of no clinical consequence for the mother, a small number of women will develop osteoporosis and suffer fragility fractures. Vertebral fractures occur most commonly in PAO and are often multiple. Due to the rarity of PAO, systematic study to date has been limited. Aetiology is poorly understood, but traditional osteoporosis risk factors and genetic factors are likely to play a role. A small number of cases may be due to an underlying metabolic bone disorder or monogenic condition. Management of PAO is challenging, due both to a poor evidence base and the fact that spontaneous improvement in BMD is known to occur once pregnancy and lactation are complete. Bisphosphonates, denosumab and teriparatide have all been used in individual patients, but the data supporting their use are currently limited.

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Source: Kovacs CM, Kronenberg HM, Endocr Rev, Volume 18, Issue 6, 1 December 1997, Pages 832–872, https://doi.org/10.1210/edrv.18.6.0319 (with permission)

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References

  1. Kovacs CS, Ralston SH (2015) Presentation and management of osteoporosis presenting in association with pregnancy or lactation. Osteoporos Int 26:2223–2241. https://doi.org/10.1007/s00198-015-3149-3

    Article  CAS  PubMed  Google Scholar 

  2. Kalkwarf HJ (2006) Calcium in pregnancy and lactation. In: Weaver CM, Heaney RP (eds) Calcium in human health. Humana Press, Totowa, pp 297–309

    Chapter  Google Scholar 

  3. Kovacs C, Kronenberg H (2013) Pregnancy and lactation. In: Rosen C (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 8th edn. Wiley-Blackwell, Ames, pp 156–164

    Chapter  Google Scholar 

  4. Kovacs C (2016) Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev 96:449–547. https://doi.org/10.1152/physrev.00027.2015

    Article  CAS  PubMed  Google Scholar 

  5. Purdie DW, Aaron JE, Selby PL (1988) Bone histology and mineral homeostasis in human pregnancy. BJOG 95:849–54. https://doi.org/10.1111/j.1471-0528.1988.tb06568.x

    Article  CAS  Google Scholar 

  6. Naylor KE, Iqbal P, Fledelius C, Fraser RB, Eastell R (2000) The effect of pregnancy on bone density and bone turnover. J Bone Miner Res 15(1):129–137. https://doi.org/10.1359/jbmr.2000.15.1.129

    Article  CAS  PubMed  Google Scholar 

  7. Ettinger AS, Lamadrid-Figueroa H, Mercado-García A, Kordas K, Wood RJ, Peterson KE, Hu H et al (2014) Effect of calcium supplementation on bone resorption in pregnancy and the early postpartum: a randomized controlled trial in Mexican Women. Nutr J 13:116. https://doi.org/10.1186/1475-2891-13-116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Møller UK, Vi Streym S, Mosekilde L, Rejnmark L (2012) Changes in bone mineral density and body composition during pregnancy and postpartum. A controlled cohort study. Osteoporos Int 23:1213–1223. https://doi.org/10.1007/s00198-011-1654-6

    Article  PubMed  Google Scholar 

  9. Breasail ÓM, Prenticel A, Ward K (2020) Pregnancy-related bone mineral and microarchitecture changes in women aged 30 to 45 years. J Bone Miner Res 35:1253–1262. https://doi.org/10.1002/jbmr.3998

    Article  CAS  Google Scholar 

  10. Rizzoli R, Bonjour JP (1997) Hormones and bones. Lancet 349:S20-23. https://doi.org/10.1016/s0140-6736(97)90007-6

    Article  Google Scholar 

  11. Pearson D, Kaur M, San P, Lawon N, Baker P, Hosking D (2004) Recovery of pregnancy mediated bone loss during lactation. Bone 34:570–578. https://doi.org/10.1016/j.bone.2003.11.005

    Article  CAS  PubMed  Google Scholar 

  12. Sowers MF, Corton G, Shapiro B, Jannausch ML, Crutchfield M, Smith ML, Randolph JF et al (1993) Changes in bone density with lactation. JAMA 269:3130–3135. https://doi.org/10.1001/jama.1993.03500240074029

    Article  CAS  PubMed  Google Scholar 

  13. Holmberg-Marttila D, Sievanen H, Laippala P, Tuimala R (2000) Factors underlying changes in bone mineral during postpartum amenorrhea and lactation. Osteoporos Int 11:570–576. https://doi.org/10.1007/s001980070077

    Article  CAS  PubMed  Google Scholar 

  14. Brembeck P, Lorentzon M, Ohlsson C, Winkvist A, Augustin H (2015) Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpartum. J Clin Endocrinol Metab 100:535–543. https://doi.org/10.1210/jc.2014-2825

    Article  CAS  PubMed  Google Scholar 

  15. Kovacs CS (2017) The skeleton is a storehouse of mineral that is plundered during lactation and (fully?) replenished afterwards. J Bone Miner Res 32:676–680. https://doi.org/10.1002/jbmr.3090

    Article  CAS  PubMed  Google Scholar 

  16. Matsumoto I, Kosha S, Noguchi S-I, Kojima N, Oki T, Douchi T, Nagata Y (1995) Changes of bone mineral density in pregnant and postpartum women. J Obstet Gynaecol (Lahore) 21:419–425. https://doi.org/10.1111/j.1447-0756.1995.tb01031.x

    Article  CAS  Google Scholar 

  17. Grizzo FMF, Alarcão ACJ, Dell’ Agnolo CM, Pedroso RB, Santos TS, Vissoci JRN, Pinheiro MM et al (2020) How does women’s bone health recover after lactation? A systematic review and meta-analysis. Osteoporos Int 31:413–427. https://doi.org/10.1007/s00198-019-05236-8

    Article  CAS  PubMed  Google Scholar 

  18. Bjørnerem Å, Ghasem-Zadeh A, Wang X, Bui M, Walker SP, Zebaze R, Seeman E (2017) Irreversible deterioration of cortical and trabecular microstructure associated with breastfeeding. J Bone Miner Res 32:681–687. https://doi.org/10.1002/jbmr.3018

    Article  PubMed  Google Scholar 

  19. Cooke-Hubley S, Gao Z, Mugford G, Kaiser SM, Goltzman D, Leslie WD, Davison KS et al (2019) Parity and lactation are not associated with incident fragility fractures or radiographic vertebral fractures over 16 years of follow-up: Canadian Multicentre Osteoporosis Study (CaMos). Arch Osteoporosis 14:49. https://doi.org/10.1007/s11657-019-0601-6

    Article  Google Scholar 

  20. Hadji P, Boekhoff J, Hahn M, Hellmeyer L, Hars O, Kyvernitakis I, Grizzo FMF et al (2017) Pregnancy-associated osteoporosis: a case-control study. Osteoporos Int 28:1393–1399. https://doi.org/10.1007/s00198-016-3897-8

    Article  CAS  PubMed  Google Scholar 

  21. Butscheidt S, Delsmann A, Rolvien T, Barvencik F, Al-Bughaili M, Mundlos S, Schinke T et al (2018) Mutational analysis uncovers monogenic bone disorders in women with pregnancy-associated osteoporosis: three novel mutations in LRP5, COL1A1, and COL1A2. Osteoporos Int 29:1643–1651. https://doi.org/10.1007/s00198-018-4499-4

    Article  CAS  PubMed  Google Scholar 

  22. Smith R, Athanasou NA, Ostlere SJ, Vipond SE (1995) Pregnancy-associated osteoporosis. QJM 88:865–878. https://doi.org/10.1093/oxfordjournals.qjmed.a069019

    Article  CAS  PubMed  Google Scholar 

  23. Kovacs CS (2014) Osteoporosis presenting in pregnancy, puerperium, and lactation. Curr Opin Endocrinol Diabetes Obes 21:468–475. https://doi.org/10.1097/MED.0000000000000102

    Article  PubMed  Google Scholar 

  24. Hardcastle SA, Yahya F, Bhalla AK (2019) Pregnancy-associated osteoporosis: a UK case series and literature review. Osteoporos Int 30(5):939–948. https://doi.org/10.1007/s00198-019-04842-w

    Article  CAS  PubMed  Google Scholar 

  25. Che H, Breuil V, Cortet B, Paccou J, Thomas T, Chapuis L, Debiais F et al (2019) Vertebral fractures cascade: potential causes and risk factors. Osteoporos Int 30:555–563. https://doi.org/10.1007/s00198-018-4793-1

    Article  CAS  PubMed  Google Scholar 

  26. Bonacker J, Janousek M, Kröber M (2014) Pregnancy-associated osteoporosis with eight fractures in the vertebral column treated with kyphoplasty and bracing: a case report. Arch Orthop Trauma Surg 134:173–179. https://doi.org/10.1007/s00402-013-1912-5

    Article  CAS  PubMed  Google Scholar 

  27. Cooper C, Atkinson EJ, MichaelO’Fallon W, Melton JL (1992) Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res 7(2):221–227. https://doi.org/10.1002/jbmr.5650070214

    Article  CAS  PubMed  Google Scholar 

  28. Kyvernitakis I, Reuter TC, Hellmeyer L, Hars O, Hadji P (2018) Subsequent fracture risk of women with pregnancy and lactation-associated osteoporosis after a median of 6 years of follow-up. Osteoporos Int 29:135–142. https://doi.org/10.1007/s00198-017-4239-1

    Article  CAS  PubMed  Google Scholar 

  29. Jun Jie Z, Ai G, Baojun W, Liang Z (2019) Intertrochanteric fracture in pregnancy- and lactation-associated osteoporosis. J Int Med Res. https://doi.org/10.1177/0300060519858013

    Article  PubMed  PubMed Central  Google Scholar 

  30. Laroche M, Talibart M, Cormier C, Roux C, Guggenbuhl P, Degboe Y (2017) Pregnancy-related fractures: a retrospective study of a French cohort of 52 patients and review of the literature. Osteoporos Int 28:3135–3142. https://doi.org/10.1007/s00198-017-4165-2

    Article  CAS  PubMed  Google Scholar 

  31. Aynaci O, Kerimoglu S, Ozturk C, Saracoglu M (2008) Bilateral non-traumatic acetabular and femoral neck fractures due to pregnancy-associated osteoporosis. Arch Orthop Trauma Surg 128:313–316. https://doi.org/10.1007/s00402-007-0439-z

    Article  PubMed  Google Scholar 

  32. Breuil V, Brocq O, Euller-Ziegler L (1997) Insufficiency fracture of the sacrum revealing a pregnancy associated osteoporosis. First Case Report Ann Rheum Dis 56:278–279. https://doi.org/10.1136/ard.56.4.278b

    Article  CAS  PubMed  Google Scholar 

  33. Tuna F, Akleylek C, Özdemir H, Demirbağ Kabayel D (2020) Risk factors, fractures, and management of pregnancy-associated osteoporosis: a retrospective study of 14 Turkish patients. Gynecol Endocrinol 36:238–242. https://doi.org/10.1080/09513590.2019.1648417

    Article  CAS  PubMed  Google Scholar 

  34. Cohen A, Kamanda-Kosseh M, Dempster DW, Zhou H, Müller R, Goff E, Colon I et al (2019) Women with pregnancy and lactation-associated osteoporosis (PLO) have low bone remodeling rates at the tissue level. J Bone Miner Res 34:1552–1561. https://doi.org/10.1002/jbmr.3750

    Article  CAS  PubMed  Google Scholar 

  35. O’Sullivan SM, Grey AB, Singh R, Reid IR (2006) Bisphosphonates in pregnancy and lactation-associated osteoporosis. Osteoporos Int 17:1008–1012. https://doi.org/10.1007/s00198-006-0112-3

    Article  CAS  PubMed  Google Scholar 

  36. Hong N, Kim JE, Lee SJ, Kim SH, Rhee Y (2018) Changes in bone mineral density and bone turnover markers during treatment with teriparatide in pregnancy- and lactation- associated osteoporosis. Clin Endocrinol 88:652–665. https://doi.org/10.1111/cen.13557

    Article  CAS  Google Scholar 

  37. Patel S (2014) Primary bone marrow oedema syndromes. Rheumatology 53:785–792. https://doi.org/10.1093/rheumatology/ket324

    Article  PubMed  Google Scholar 

  38. Funk J, Shoback D, Genant H (1995) Transient osteoporosis of the hip in pregnancy: natural history of changes in bone mineral density. Clin Endocrinol 43:373–382. https://doi.org/10.1111/j.1365-2265.1995.tb02046.x

    Article  CAS  Google Scholar 

  39. Anai T, Urata K, Mori A, Miyazaki F, Okamoto S (2013) Transient osteoporosis of the hip in pregnancy associated with generalized low bone mineral density-a case report. Gynecol Obstet Invest 76:133–138. https://doi.org/10.1159/000351564

    Article  PubMed  Google Scholar 

  40. Phillips AJ, Ostlere SJ, Smith R (2000) Pregnancy-associated osteoporosis: Does the skeleton recover? Osteoporos Int 11:449–454. https://doi.org/10.1007/s001980070113

    Article  CAS  PubMed  Google Scholar 

  41. Cerit ET, Cerit M (2020) A case of pregnancy and lactation associated osteoporosis in the third pregnancy; robust response to teriparatide despite delayed administration. Bone Rep 13:100706. https://doi.org/10.1016/j.bonr.2020.100706

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sanchez A, Zanchetta MB, Danilowicz K (2016) Two cases of pregnancy- and lactation-associated osteoporosis successfully treated with denosumab. Clin Cases Miner Bone Metab 13:244–246. https://doi.org/10.11138/ccmbm/2016.13.3.244

    Article  PubMed  Google Scholar 

  43. Dunne F, Walters B, Marshall T, Heath DA (1993) Pregnancy associated osteoporosis. Clin Endocrinol (Oxf) 39:487–490. https://doi.org/10.1111/j.1365-2265.1993.tb02398.x

    Article  CAS  Google Scholar 

  44. Campos-Obando N, Oei L, Hoefsloot LH, Kiewiet RM, Klaver CCW, Simon MEH, Carola Zillikens M (2014) Osteoporotic vertebral fractures during pregnancy: be aware of a potential underlying genetic cause. J Clin Endocrinol Metab 99:1107–1111. https://doi.org/10.1210/jc.2013-3238

    Article  CAS  PubMed  Google Scholar 

  45. Cook FJ, Mumm S, Whyte MP, Wenkert D (2014) Pregnancy-associated osteoporosis with a heterozygous deactivating LDL receptor-related protein 5 (LRP5) mutation and a homozygous methylenetetrahydrofolate reductase (MTHFR) polymorphism. J Bone Miner Res 29:922–928. https://doi.org/10.1002/jbmr.2095

    Article  CAS  PubMed  Google Scholar 

  46. Peris P, Guañabens N, Monegal A, Pons F, Martínez de Osaba MJ, Ros I, Muñoz-Gómez J (2002) Pregnancy associated osteoporosis: the familial effect. Clin Exp Rheumatol 20(5):697–700

    CAS  PubMed  Google Scholar 

  47. Grizzo FMF, da Silva MJ, Pinheiro MM, Jorgetti V, Carvalho MDB, Pelloso SM (2015) Pregnancy and lactation-associated osteoporosis: bone histomorphometric analysis and response to treatment with zoledronic acid. Calcif Tissue Int 97:421–425. https://doi.org/10.1007/s00223-015-0028-z

    Article  CAS  PubMed  Google Scholar 

  48. Bayram S, Ozturk C, Sivrioglu K, Aydinli U, Kucukoglu S (2006) Kyphoplasty for pregnancy-associated osteoporotic vertebral fractures. Jt Bone Spine 73:564–566. https://doi.org/10.1016/j.jbspin.2005.11.015

    Article  Google Scholar 

  49. Li LJ, Zhang J, Gao P, Lv F, Song YW, Chang XY, Zhao DC et al (2018) Clinical characteristics and bisphosphonates treatment of rare pregnancy- and lactation-associated osteoporosis. Clin Rheumatol 37:3141–3150. https://doi.org/10.1007/s10067-018-4185-0

    Article  PubMed  Google Scholar 

  50. Hellmeyer L, Kühnert M, Ziller V, Schmidt S, Hadji P (2007) The use of i. v. bisphosphonate in pregnancy-associated osteoporosis—case study. Exp Clin Endocrinol Diabetes 115:139–142. https://doi.org/10.1055/s-2007-967091

    Article  CAS  PubMed  Google Scholar 

  51. Naylor KE, Bradburn M, Paggiosi MA, Gossiel F, Peel NFA, McCloskey EV, Walsh JS et al (2018) Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density. Osteoporos Int 29:1407–1417. https://doi.org/10.1007/s00198-018-4460-6

    Article  CAS  PubMed  Google Scholar 

  52. Ioannis SP, Chrysoula LG, Aikaterini K, George T, George LP, Nikolaos PA, Symeon T et al (2011) The use of bisphosphonates in women prior to or during pregnancy and lactation. Hormones 10:280–291. https://doi.org/10.14310/horm.2002.1319

    Article  Google Scholar 

  53. Ornoy A, Wajnberg R, Diav-Citrin O (2006) The outcome of pregnancy following pre-pregnancy or early pregnancy alendronate treatment. Reprod Toxicol 22:578–579. https://doi.org/10.1016/j.reprotox.2006.05.009

    Article  CAS  PubMed  Google Scholar 

  54. Levy S, Fayez I, Taguchi N, Han JY, Aiello J, Matsui D, Moretti M et al (2009) Pregnancy outcome following in utero exposure to bisphosphonates. Bone 44:428–430. https://doi.org/10.1016/j.bone.2008.11.001

    Article  CAS  PubMed  Google Scholar 

  55. Vujasinovic-Stupar N, Pejnovic N, Markovic L, Zlatanovic M (2012) Pregnancy-associated spinal osteoporosis treated with bisphosphonates: Long-term follow-up of maternal and infants outcome. Rheumatol Int 32:819–823. https://doi.org/10.1007/s00296-011-1816-z

    Article  PubMed  Google Scholar 

  56. Ijuin A, Yoshikata H, Asano R, Tsuburai T, Kikuchi R, Sakakibara H (2017) Teriparatide and denosumab treatment for pregnancy and lactation-associated osteoporosis with multiple vertebral fractures: a case study. Taiwan J Obstet Gynecol 56:863–866. https://doi.org/10.1016/j.tjog.2017.10.028

    Article  PubMed  Google Scholar 

  57. Stumpf UC, Kurth AA, Windolf J, Fassbender WJ (2007) Pregnancy-associated osteoporosis: an underestimated and underdiagnosed severe disease. A review of two cases in short- and long-term follow-up. Adv Med Sci 52:94–97

    CAS  PubMed  Google Scholar 

  58. Choe EY, Song JE, Park KH, Seok H, Lee EJ, Lim SK, Rhee Y (2012) Effect of teriparatide on pregnancy and lactation-associated osteoporosis with multiple vertebral fractures. J Bone Miner Metab 30(5):596–601. https://doi.org/10.1007/s00774-011-0334-0

    Article  CAS  PubMed  Google Scholar 

  59. Hellmeyer L, Boekhoff J, Hadji P (2010) Treatment with teriparatide in a patient with pregnancy-associated osteoporosis. Gynecol Endocrinol 26:725–728. https://doi.org/10.3109/09513591003649831

    Article  CAS  PubMed  Google Scholar 

  60. Lee SH, Hong M-K, Park SW, Park H-M, Kim J, Ahn J (2013) A case of teriparatide on pregnancy-induced osteoporosis. J Bone Metab. 20(2):111–114. https://doi.org/10.11005/jbm.2013.20.2.111

    Article  PubMed  PubMed Central  Google Scholar 

  61. Nasto LA, Pambianco V, Autore G, Colangelo D, Pontecorvi A, Pola E (2017) Multiple vertebral fractures in three young women with acute postpartum osteoporosis: Description and treatment. Glob Spine J 7(2):P287. https://doi.org/10.1177/2192568217708189

    Article  Google Scholar 

  62. Pola E, Colangelo D, Nasto LA, Pambianco V, Autore G, Formica VM, Maccauro G (2016) Pregnancy-associated osteoporosis (pao) with multiple vertebral fragility fractures: diagnosis and treatment in a young primigravid woman. J Biol Regul Homeost Agents 30(4 Suppl 1):153–158

    CAS  PubMed  Google Scholar 

  63. Lampropoulou-Adamidou K, Trovas G, Stathopoulos IP, Papaioannou NA (2012) Case report: teriparatide treatment in a case of severe pregnancy-and lactation- associated osteoporosis. Hormones 11:495–500. https://doi.org/10.14310/horm.2002.1383

    Article  PubMed  Google Scholar 

  64. Cohen A, Kamanda-Kosseh M, Recker RR, Lappe JM, Dempster DW, Zhou H, Cremers S et al (2015) Bone density after teriparatide discontinuation in premenopausal idiopathic osteoporosis. J Clin Endocrinol Metab 100(11):4208–4214. https://doi.org/10.1210/jc.2015-2829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tanriover MD, Oz SG, Sozen T, Kilicarslan A, Guven GS (2009) Pregnancy- and lactation-associated osteoporosis with severe vertebral deformities: can strontium ranelate be a new alternative for the treatment? Spine J 9:e20–e24. https://doi.org/10.1016/j.spinee.2008.06.451

    Article  PubMed  Google Scholar 

  66. Tanriover MD, Oz SG, Sozen T (2015) Ten-year follow-up in pregnancy and lactation-associated osteoporosis: sequential therapy with strontium ranelate and ibandronate. Spine J 15(5):1164–1165. https://doi.org/10.1016/j.spinee.2014.10.022

    Article  PubMed  Google Scholar 

  67. Zarattini G, Buffoli P, Isabelli G, Marchese M (2014) Pregnancy-associated osteoporosis with seven vertebral compression fractures, a case treated with strontium ranelate. Clin Cases Miner Bone Metab 11:139–141. https://doi.org/10.11138/ccmbm/2014.11.2.139

    Article  PubMed  PubMed Central  Google Scholar 

  68. Ebeling PR, Akesson K, Bauer DC, Buchbinder R, Eastell R, Fink HA, Giangregorio L et al (2019) The efficacy and safety of vertebral augmentation: a second ASBMR task force report. J Bone Miner Res 34(1):3–21. https://doi.org/10.1002/jbmr.3653

    Article  PubMed  Google Scholar 

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SH is grateful to Dr Ashok Bhalla for his helpful comments on the manuscript.

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    Sarah A. Hardcastle

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SH received conference fee funding from Lilly (UK) in 2018.

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Hardcastle, S.A. “Pregnancy and Lactation Associated Osteoporosis”. Calcif Tissue Int 110, 531–545 (2022). https://doi.org/10.1007/s00223-021-00815-6

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