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Response to "Letter to the editor: Labral calcification plays a key role in hip pain and symptoms in femoroacetabular impingement".
Journal of Orthopaedic Surgery and Research ( IF 2.8 ) Pub Date : 2020-07-22 , DOI: 10.1186/s13018-020-01799-z
Giovanni Trisolino 1 , Marta Favero 2 , Dante Dallari 3 , Enrico Tassinari 4 , Francesco Traina 4 , Miguel Otero 5 , Steven R Goldring 5 , Mary B Goldring 5 , Chiara Carubbi 3 , Roberta Ramonda 2 , Stefano Stilli 1 , Brunella Grigolo 6 , Eleonora Olivotto 6
Affiliation  

Dear Editor,

We are writing in reply to Dr. Zhong’s comments regarding our recent publication [1]. While we appreciate the discussion and feedback, we are also concerned that some of these comments are somewhat vague and may be misleading. Our specific replies to Dr. Zhong’s comments are appended below.

We thank Drs. Zhong and Ouyang for reading our work and for the discussion. We enclosed a point-by-point response to their questions.

Firstly, we acknowledge that the lack of samples of healthy controls is an important limitation to our paper. Unfortunately, the Italian law and the IOR ethical committee do not allow for tissue sampling from donors for research purposes. So, we can obtain fresh samples from donors only in case they were not used during the operation after assignment. The same limitation was mentioned in a previous paper from our group, concerning fresh menisci from donors [2]. Concerning the present study, this issue is further complicated by the fact that samples of labrum from donors should be matched by age and sex with samples from patients with FAI. In our opinion, age-matching is a critical aspect since we believe that comparing labrum from young FAI patients with “healthy” aged donors could be misleading.

We should point that the FAI patients enrolled in our study had a mean age of 33 years as opposed to 62 years in the work mentioned by Drs. Zhong and Ouyang [3]. These significant differences in age should be considered when trying to compare “healthy” and “FAI” labral tissues. The “physiological process” hypothesized by the commenters could be due to aging, so it should not be present in young adults. More importantly, as clearly stated in the abstract and throughout the manuscript, our work focused on the association between labrum and synovium (and other joint tissues) in patients with femoroacetabular impingement (FAI) and the impact of these changes on surgical outcomes. Therefore, comparisons with healthy tissues were out of the scope of this study. Nonetheless, our research is ongoing (we have had just some delay due to the COVID-19 pandemic); these aspects will be presented in an upcoming article.

Concerning the second comment, Dr. Zhong’s speculation is biased by the erroneous assumption that FAI (and consequently the labral tear) is limited to the anterosuperior region. We have extensively explained in the manuscript that we collected 6 cases with isolated CAM deformity, 3 cases with isolated Pincer, and 12 mixed cases. We found that labral damage was not always and not only limited to the anterior-superior region but sometimes involved the entire labrum. However, the specimens were taken by debrided labral tissues from the most damaged labral zone. We could not collect multiple random samples from apparently “healthy” zones of labrum because it was unfeasible from an ethical point of view. Therefore, we cannot assure that the histopathological features of the specimen correspond with the characteristics of the entire labrum.

Hubert et al. [4] stained all samples with von Kossa to confirm “calcium-phosphate deposition,” and alizarin red is well-established alternative to stain “calcium-phosphate deposition” in joint tissues. We agree that the detection of BCP crystals is particularly difficult, and to distinguish BCP and CPPD, we require additional measurements, like polarized or transmission electron microscopy [5, 6]. Our ongoing studies (in collaboration with Dr. Oliviero [7]) aim to further characterize the nature of calcium deposits in FAI and OA patients, in line with Dr. Favero’s (co-author in this study) expertise and research interest. We hope to report these findings soon.

Previous study stated that the amount of calcification in the labrum instead of histological degeneration grade had significant influence on the preoperative Harris Hip Score (HHS) in patients with end-stage OA [3, 4]. Therefore, how much amount of calcium crystal deposition in the labrum produce adverse effect on hip function in patients with FAI needs further study.

This is already mentioned in the Discussion “higher local concentration of calcium crystal deposition in the labrum could lead to increased release of nociceptor stimulating substances within the fibrocartilage tissue, which densely innervated” along with pertinent references. Unfortunately, the study is not powered to establish a statistically significant threshold of calcium crystals deposition in the labrum.

Sincerely,

Giovanni Trisolino,

Marta Favero,

Enrico Tassinari,

Eleonora Olivotto

  1. 1.

    Trisolino G, Favero M, Dallari D, Tassinari E, Traina F, Otero M, et al. Labral calcification plays a key role in hip pain and symptoms in femoroacetabular impingement. J OrthopSurg Res. 2020;15(1):86.

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    Battistelli M, Favero M, Burini D, Trisolino G, Dallari D, De Franceschi L, et al. Morphological and ultrastructural analysis of normal, injured and osteoarthritic human knee menisci. Eur J Histochem. 2019;63(1):2998.

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    Hawellek T, Hubert J, Hischke S, Krause M, Bertrand J, Schmidt BC, et al. Calcification of the acetabular labrum of the hip: prevalence in the general population and relation to hip articular cartilage and fibrocartilage degeneration. Arthritis ResTher. 2018;20(1):104.

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    Hubert J, Hawellek T, Moe M, Hischke S, Krause M, Rolvien T, et al. Labral calcification in end-stage osteoarthritis of the hip correlates with pain and clinical function. J Orthop Res. 2018;36(4):1248–55.

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    Yavorskyy A, Hernandez-Santana A, McCarthy G, McMahon G. Detection of calcium phosphate crystals in the joint fluid of patients with osteoarthritis – analytical approaches and challenges. Analyst. 2008;133:302–18.

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    Frallonardo P, Oliviero F, Peruzzo L, Tauro L, Scanu A, Galozzi P, et al.. Detection of calcium crystals in knee osteoarthritis synovial fluid: a comparison between polarized light and scanning electron microscopy. J of Clin Rheumatol 2018 October 2016 - Volume 22 - Issue 7 - p 369-371.

  7. 7.

    Oliviero F, Galozzi P, Ramonda R, LeitedeOliveiraF, Schiavon F, Scanu A et al. Unusual findings in synovial fluid analysis: a review. Ann Clin Lab Sci. May-June 2017;47(3):253-259).

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Affiliations

  1. Pediatric Orthopedic and Traumatology, IRCCS Istituto Ortopedico Rizzoli, via G.C.Pupilli 1, 40136, Bologna, Italy

    Giovanni Trisolino & Stefano Stilli

  2. Rheumatology Unit, Department of Medicine (DIMED), University Hospital of Padova, Via Giustiniani 2, 35128, Padua, Italy

    Marta Favero & Roberta Ramonda

  3. Reconstructive Orthopaedic Surgery Innovative Techniques - Musculoskeletal Tissue Bank; Revision surgery of hip prosthesis and development of new implants, IRCCS Istituto Ortopedico Rizzoli, via G.C.Pupilli 1, 40136, Bologna, Italy

    Dante Dallari & Chiara Carubbi

  4. Orthopaedic-Traumatology and Prosthetic surgery and revisions of hip and knee implants, IRCCS Istituto Ortopedico Rizzoli, via G.C.Pupilli 1, 40136, Bologna, Italy

    Enrico Tassinari & Francesco Traina

  5. HSS Research Institute, Hospital for Special Surgery, 535 E 70th St, New York, NY, 10021, USA

    Miguel Otero, Steven R. Goldring & Mary B. Goldring

  6. RAMSES Laboratory, RIT Department, IRCCS Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136, Bologna, Italy

    Brunella Grigolo & Eleonora Olivotto

  7. Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136, Bologna, Italy

    Eleonora Olivotto

Authors
  1. Giovanni TrisolinoView author publications

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  2. Marta FaveroView author publications

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  3. Dante DallariView author publications

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  4. Enrico TassinariView author publications

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  5. Francesco TrainaView author publications

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  6. Miguel OteroView author publications

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  7. Steven R. GoldringView author publications

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  8. Mary B. GoldringView author publications

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  9. Chiara CarubbiView author publications

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  10. Roberta RamondaView author publications

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  11. Stefano StilliView author publications

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  12. Brunella GrigoloView author publications

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  13. Eleonora OlivottoView author publications

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Contributions

EO, GT, MF: concept, writing, and revising. All authors have read and approved the final manuscript

Corresponding author

Correspondence to Marta Favero.

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Trisolino, G., Favero, M., Dallari, D. et al. Response to “Letter to the editor: Labral calcification plays a key role in hip pain and symptoms in femoroacetabular impingement”. J Orthop Surg Res 15, 274 (2020). https://doi.org/10.1186/s13018-020-01799-z

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中文翻译：
对“致编辑的信：唇钙化在股骨髋臼撞击的髋部疼痛和症状中起关键作用”。

亲爱的编辑，

我们写信是为了回应钟博士对我们最近的出版物[1]的评论。在赞赏讨论和反馈的同时，我们也担心其中一些评论有些含糊，可能会产生误导。我们对钟博士的评论的具体答复如下。

我们感谢博士。钟和欧阳阅读了我们的作品并进行了讨论。我们附上对他们问题的逐点回答。

首先，我们承认缺乏健康对照样品是我们论文的重要限制。不幸的是，意大利法律和IOR伦理委员会不允许出于研究目的从捐赠者那里进行组织采样。因此，只有在分配后的手术中没有使用捐赠者的情况下，我们才能从捐赠者那里获得新鲜样本。我们小组先前的一篇论文提到了同样的局限性，涉及捐赠者的新半月板[2]。关于本研究，由于供体的唇lab样本应按年龄和性别与FAI患者的样本匹配，这一事实使问题变得更加复杂。我们认为，年龄匹配是至关重要的方面，因为我们认为将年轻的FAI患者的唇lab肌与“健康的”老年供体进行比较可能会产生误导。

我们应该指出，参加本研究的FAI患者的平均年龄为33岁，而Drs提到的工作为62岁。钟和欧阳[3]。在尝试比较“健康”和“ FAI”的唇部组织时，应考虑年龄上的这些显着差异。评论者假设的“生理过程”可能是由于衰老造成的，因此年轻人中不应出现该过程。更重要的是，正如摘要和整篇文章中明确指出的那样，我们的工作重点是股骨髋臼撞击（FAI）患者的唇骨和滑膜（及其他关节组织）之间的关联以及这些变化对手术结局的影响。因此，与健康组织的比较超出了本研究的范围。尽管如此，我们的研究仍在进行中（由于COVID-19大流行，我们才有所延误）；这些方面将在以后的文章中介绍。

关于第二条评论，钟博士的推测被误认为FAI（以及由此引起的唇裂）仅限于上前区。我们在手稿中进行了广泛的解释，收集了6例孤立CAM畸形，3例孤立Pincer和12例混合病例。我们发现，唇部损害并不总是而且不仅限于前上区，有时甚至涉及整个唇部。但是，标本是从受损程度最大的唇部区域清创的唇部组织取得的。我们不能从明显“健康”的唇部区域收集多个随机样本，因为从伦理的角度来看这是不可行的。因此，我们不能保证标本的组织病理学特征与整个唇唇的特征一致。

休伯特等。[4]用冯·科萨（von Kossa）对所有样品进行染色，以确认“磷酸钙沉积”，而茜素红是在关节组织中染色“磷酸钙沉积”的公认替代方法。我们同意检测BCP晶体特别困难，并且要区分BCP和CPPD，我们需要进行额外的测量，例如极化或透射电子显微镜[5，6]。我们正在进行的研究（与Oliviero博士[7]合作）旨在根据Favero博士（本研究的合著者）的专业知识和研究兴趣，进一步表征FAI和OA患者中钙沉积的性质。我们希望尽快报告这些发现。

先前的研究表明，终末期OA患者的唇骨钙化量而非组织学变性程度对术前Harris Hip Score（HHS）有重要影响[3，4]。因此，在FAI患者的唇中有多少钙晶体沉积会对髋关节功能产生不利影响。

讨论中已经提到“在唇唇中较高的局部钙晶体沉积浓度可能导致纤维软骨组织中伤害感受器刺激性物质的释放增加，神经刺激性物质被密集地支配”以及相关参考文献。不幸的是，该研究无力建立统计上在唇唇中钙晶体沉积的阈值。

真诚的

乔凡尼·特里索里诺（Giovanni Trisolino），

Marta Favero，

恩里科·塔西纳里（Enrico Tassinari），

Eleonora Olivotto

  1. 1。

    Trisolino G，Favero M，Dallari D，Tassinari E，Traina F，Otero M等。唇钙化在股骨髋臼撞击中的髋部疼痛和症状中起关键作用。J OrthopSurg研究。2020; 15（1）：86。

    谷歌学术

  2. 2。

    Battistelli M，Favero M，Burini D，Trisolino G，Dallari D，De Franceschi L等。正常，受伤和骨关节炎的人类半月板的形态和​​超微结构分析。Eur J Histochem。2019; 63（1）：2998。

    文章Google学术搜索

  3. 3。

    Hawellek T，Hubert J，Hischke S，Krause M，Bertrand J，Schmidt BC等。髋臼髋臼钙化：一般人群中的患病率及其与髋关节软骨和纤维软骨变性的关系。关节炎治疗。2018; 20（1）：104。

    文章Google学术搜索

  4. 4。

    Hubert J，Hawellek T，Moe M，Hischke S，Krause M，Rolvien T等。髋关节终末期骨关节炎的唇钙化与疼痛和临床功能有关。J Orthop水库。2018; 36（4）：1248–55。

    PubMed Google学术搜索

  5. 5，

    Yavorskyy A，Hernandez-Santana A，McCarthy G，McMahonG。骨关节炎患者关节液中磷酸钙晶体的检测-分析方法和挑战。分析师。2008; 133：302-18。

    文章Google学术搜索

  6. 6。

    Frallonardo P，Oliviero F，Peruzzo L，Tauro L，Scanu A，Galozzi P等人。膝关节骨关节炎滑液中钙晶体的检测：偏振光和扫描电子显微镜之间的比较。临床风湿病学杂志2018年10月2016年-第22卷-第7期-369-371页。

  7. 7。

    Oliviero F，Galozzi P，Ramonda R，LeitedeOliveiraF，Schiavon F，Scanu A等。滑液分析中的异常发现：综述。安临床实验室科学。2017年5月至6月; 47（3）：253-259）。

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隶属关系

  1. IRCCS Istituto Ortopedico Rizzoli的小儿骨伤科，通过GCPupilli 1，40136，Bologna，Italy

    乔凡尼·特里索里诺（Giovanni Trisolino）和斯特凡诺·斯蒂利（Stefano Stilli）

  2. 帕多瓦大学医院医学部风湿病科（DIMED），意大利帕多瓦Via Giustiniani 2，35128

    Marta Favero和Roberta Ramonda

  3. 重建骨科手术创新技术-肌肉骨骼组织库；髋关节假体的翻修手术和新植入物的研发，IRCCS Istituto Ortopedico Rizzoli，通过GCPupilli 1，40136，意大利博洛尼亚，

    但丁·达拉里（Dante Dallari）和基亚拉·卡鲁比（Chiara Carubbi）

  4. IRCCS Istituto Ortopedico Rizzoli的骨科-创伤外科和修复外科以及髋关节和膝关节植入物的修复，通过GCPupilli 1，40136，意大利博洛尼亚

    恩里科·塔西纳里（Enrico Tassinari）和弗朗切斯科·特拉纳（Francesco Traina）

  5. 10021美国纽约州纽约市70街535号特殊外科医院HSS研究所

    Miguel Otero，Steven R. Goldring和Mary B. Goldring

  6. IRCCS Istituto Ortopedico Rizzoli RITCS RIT部门RAMSES实验室，通过di Barbiano 1/10，40136，Bologna，Italy

    布鲁内拉·格里戈洛（Brunella Grigolo）和埃莉奥诺拉（Eleonora Olivotto）

  7. IRCCS Istituto Ortopedico Rizzoli免疫血液流变学和组织再生实验室，地址：意大利迪亚·巴贝亚诺1/10，40136，博洛尼亚，意大利

    Eleonora Olivotto

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Trisolino，G.，Favero，M.，Dallari，D。等。对“致编辑的信：唇钙化在股骨髋臼撞击的髋部疼痛和症状中起关键作用”。Ĵ骨科外科杂志RES 15， 274（2020）。https://doi.org/10.1186/s13018-020-01799-z

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  • DOI ：https ：//doi.org/10.1186/s13018-020-01799-z
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