Is vitamin D deficiency behind the scenes for high incidence of Giant cell tumor amongst the Indian population? Unraveling the vitamin D - RANKL association.

INTRODUCTION: 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. HYPOTHESIS: 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)D3 levels amongst the matched control population data. MATERIALS AND RESULTS: 130 patients of primary GCTBs were matched to 310 controls from the general health check population and serum levels of 25(OH)D3 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). DISCUSSION: 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.

Giant cell tumours in fingers among the Inuit population in Greenland.

OBJECTIVE: Giant cell tumours (GCTs) of the tendon sheets in fingers are rare. We therefore find it of interest to report on 5 cases identified in the Inuit population in Greenland within 16 months prior to this study. MATERIAL AND METHODS: The Inuit account for 56,000 people of the total population in Greenland. From November 2010 to 16 months prior to this study, we diagnosed 5 cases (0.6% of all orthopaedic operations) with a GCT of the flexor tendon sheet of a finger. The patients were aged between 10 and 54 years, and 4 were women. All of them had noticed slow-growing tumours over 3 or more years and were referred for a suspected ganglion. RESULTS: In two cases, the tumour was located at the distal interphalangeal (DIP) joint in the thumb and in one case at the third finger. Two other patients had tumours at the metacarpophalangeal (MCP) joint of the third finger and the thumb, respectively; one of these two had a communicating tumour to the DIP joint. The last patient had two tumours on the same finger, one at the MCP joint and the other at the DIP joint. In one case, the tumour had also eroded the cortex of the first phalanx of the thumb, and the largest tumour measured 5 cm. CONCLUSION: GCTs of the flexor tendon sheets in fingers are rare. It could be a coincidence that we have seen 5 cases within a short period of time. It is not possible to identify past cases through a register. A tumour in a finger is not the most common location for a ganglion, especially not at the DIP level. Therefore, a large tumour at this location is more likely to be a GCT.