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Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature., Objective: We investigated a 57-year-old woman with progressive low back pain., Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer., Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved., Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

Background: This study aimed to explore the possible association between osteonecrosis of the jaws (ONJ) and oral alendronate or raloxifene used for osteoporosis and to estimate its absolute and attributable risks in the Taiwanese population., Methods: Using an electronic medical records system and manual confirmation of ONJ, we identified patients who began taking alendronate or raloxifene for osteoporosis and developed ONJ between January 2000 and April 2012., Results: The incidence of ONJ associated with oral alendronate for the management of osteoporosis began after 1 year of drug exposure and progressively increased with longer durations of therapy, specifically from 0.23% to 0.92% as the duration of treatment went from 2 years to 10 years. The overall frequency of ONJ related to oral alendronate over a 12-year period was 0.55%. The incidence rate of ONJ attributed to alendronate exposure was 283 per 100 000 persons per year. On multivariate Cox proportional analysis, adjusting for the potential confounders, alendronate remains an independent predictor for ONJ occurrence [hazard ratio 7.42 (1.02-54.09)] compared with raloxifene. Advanced age, drug duration, and coexisting diabetes and rheumatoid arthritis are contributing factors to the development of oral alendronate-related ONJ., Conclusion: We provided the evidence to support the association of ONJ with oral alendronate used in the treatment or prevention of osteoporosis.

Context: Bisphosphonates effectively increase bone mineral density and reduce fracture risk in patients with osteoporosis, but there are concerns about osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFFs) in the long-term users. So far both complications have not been reported as occurring simultaneously in an osteoporotic individual on oral alendronate., Objective: The aim of this study was to report a postmenopausal woman presenting with concomitant ONJ and AFF on oral alendronate treatment. SUBJECT, MEASURES, AND RESULT: The patient was a 63-year-old woman with a history of rheumatoid arthritis for 30 years and diabetes for 3 years. Spinal compression fractures at levels L3 and L4 were documented, and she took alendronate 70 mg weekly for 7 years. She is the first case whose dental periapical imaging and pelvic radiography documented her ONJ and AFF, which developed subsequently within 6 months., Conclusions: This case report supports the association of both ONJ and AFF with long-term oral bisphosphonate therapy.

Background: Familial hypoparathyroidism may be caused by mutations of several genes. The CaSR and GATA3 genes are the two candidates most commonly responsible for this condition., Objectives: We collected five unrelated families with familial hypoparathyroidism and examined their CaSR and GATA3 genes., Methods: Blood samples from these five families and 50 ethnically matched unrelated controls were acquired. Biochemistry screening and formal audiogram were performed to evaluate the affected individuals. All the exons and exon-intron boundaries of the GATA3 and CaSR genes were sequenced., Results: We identified three novel mutations in the GATA3 gene responsible for familial hypoparathyroidism and deafness: 1) a frameshift deletion occurring in codon 160 (478delG) was hypothesized to disrupt dual zinc fingers as well as one transactivating domain; 2) a donor splice site mutation at exon 4/intron 4 boundary (IVS4 + 2 T to GCTTACTTCCC) was predicted to lead to truncated GATA3 proteins that lack both N- and C-terminal zinc-containing fingers; and 3) a missense mutation R353S was predicted to disrupt the helical turn and thus changed the angle between the C-terminal zinc finger and the adjacent C-terminal tail. Except for a previously described polymorphism, G990R, we did not find any genetic variants in the CaSR gene., Conclusions: This is the first article presenting mutations of the GATA3 gene responsible for familial hypoparathyroidism and deafness in the Chinese population. Our results expand the spectrum of mutations and report the first splice donor site mutation of the GATA3 gene. In contrast, we do not find causal sequence variants of the CaSR gene from our collection of familial hypoparathyroidism.