Orthopedic Oncology, P. D. Hinduja Hospital and Medical Research Center, Mumbai, India.
Orthopedic Oncology, P. D. Hinduja Hospital and Medical Research Center, Mumbai, India.
Med Hypotheses. 2019 Feb;123:67-71. doi: 10.1016/j.mehy.2018.12.010. Epub 2018 Dec 21.
The major neoplastic and proliferative component of GCTB is the stromal tumor cells; that they have shown no evidence of bone destruction, instead the massive tissue destruction appears to be a result of tumor induced osteoclastogenesis. The discovery of receptor activator of nuclear factor kB (RANK) and RANK binding ligand (RANKL) uncovered the bone homeostasis and molecular mechanism by which multiple compounds (including vitamin D) regulated osteoclast differentiation; a function mediated by osteoblastic cells and osteoclast-precursor cells.
In a country burdened by vitamin D deficiency, causal relation between hypovitaminosis D and GCTB was hypothesized based on the vitamin D mediated RANKL expression and osteoclastogenesis, as India is also a population with higher incidence of GCTB as compared to Western populations described in the literature. The possibility of vitamin D regulated osteoclastogenesis in GCTB is postulated on the evidence from molecular research linking it to the RANK/RANKL/OPG pathway. The aim of this study was to analyse the prevalence of Vitamin D deficiency in patients with primary GCTB and to elucidate any difference in serum Vitamin 25(OD)D levels amongst the matched control population data.
130 patients of primary GCTBs were matched to 310 controls from the general health check population and serum levels of 25(OH)D were analyzed. Statistical analysis performed on the non-parametric data and Mann Whitney U Test used to derive inference with significance set at p < 0.05. 56 females and 76 males with median Vitamin D level in the GCTB group was 15.9 ng/ml (Mean 19.41; Range 1.03 to 92) as compared to the control population with median level of 22.2 ng/ml (Mean 25.1; Range 2.6 to 87.9). The results were significant (p value < 0.05) as compared to the control population in all decades except the third decade (p value 0.0548).
The differential expression of RANKL and OPG in response to levels of vitamin D has been established. The stromal cells of osteolytic GCTB express high levels of RANKL, which is a key signal regulator in development of this disease and bone destruction typical of GCTBs. This has resulted in research targeting this pathway for therapeutic approach in GCTBs. As vitamin D supplementation is simple and safe, increased awareness to assess and if necessary correct vitamin D status of patients is warranted, however the question as to whether patients with low vitamin D levels are more prone to develop GCTB and thus would profit from vitamin D supplementation remains unanswered. To conclude, it is essential to assess vitamin D levels in patients with GCTB as deficiency is pronounced. Future research on this hypothesis might lead to an association between Vitamin D deficiency and the onset/natural history of GCTB that may in the future help us cure or prevent GCTBs.
GCTB 的主要肿瘤和增殖成分是基质肿瘤细胞；它们没有表现出骨破坏的证据，相反，大量的组织破坏似乎是肿瘤诱导破骨细胞生成的结果。核因子 kB（RANK）受体激活剂和 RANK 结合配体（RANKL）的发现揭示了骨内稳态以及多种化合物（包括维生素 D）调节破骨细胞分化的分子机制；成骨细胞和破骨细胞前体细胞介导的功能。
在一个饱受维生素 D 缺乏症困扰的国家，根据维生素 D 介导的 RANKL 表达和破骨细胞生成，假设维生素 D 缺乏症与 GCTB 之间存在因果关系，因为与文献中描述的西方人群相比，印度也是 GCTB 发病率较高的人群。在分子研究将其与 RANK/RANKL/OPG 途径联系起来的证据的基础上，推测 GCTB 中维生素 D 调节的破骨细胞生成的可能性。本研究的目的是分析原发性 GCTB 患者中维生素 D 缺乏症的患病率，并阐明匹配对照组人群数据中血清维生素 25（OD）D 水平的差异。
将 130 例原发性 GCTB 患者与一般健康检查人群中的 310 例对照进行匹配，并分析 25（OH）D 血清水平。对非参数数据进行统计分析，并使用曼-惠特尼 U 检验得出推断，显著性水平设为 p<0.05。GCTB 组中 56 名女性和 76 名男性的中位维生素 D 水平为 15.9ng/ml（均值 19.41；范围 1.03-92），而对照组的中位水平为 22.2ng/ml（均值 25.1；范围 2.6-87.9）。与对照组相比，除第三十年外（p 值为 0.0548），所有十年的结果均具有统计学意义（p 值<0.05）。
已经确定了 RANKL 和 OPG 对维生素 D 水平的差异表达。溶骨性 GCTB 的基质细胞表达高水平的 RANKL，这是该疾病发展和 GCTB 典型骨破坏的关键信号调节剂。这导致了针对该途径的研究，作为 GCTB 的治疗方法。由于维生素 D 补充简单安全，因此需要提高对评估和必要时纠正患者维生素 D 状态的认识，但是维生素 D 水平低的患者是否更容易患上 GCTB，从而从维生素 D 补充中获益，这一问题仍未得到解答。总之，评估 GCTB 患者的维生素 D 水平至关重要，因为缺乏症很明显。关于该假设的进一步研究可能会导致维生素 D 缺乏与 GCTB 发病/自然史之间的关联，这可能有助于我们在未来治愈或预防 GCTB。
