Abstract Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and higher risk of osteoporotic fractures. Denosumab is a RANK-ligand inhibitor that prevents osteoporosis-related fractures. No previous published studies have specifically evaluated denosumab treatment of osteoporosis patients with IHC. Methods: Retrospective chart review from a private endocrinology clinic identified 31 consecutive patients with osteoporosis (prior fragility fracture and/or t-score ≤-2.5 on bone density scan) with concomitant diagnosis of IHC (defined as urine calcium > 4.0 mg/kg weight/d when intaking low-moderate calcium amounts), who had received at least 3 denosumab injections. Comparisons were made for BMD measurements determined by dual-energy x-ray absorptiometry done before denosumab initiation, and after the latest dose. Results: There were 28 women and 3 men, with average age of 71.9 ± 8.9 years. 20 subjects had prior total of 31 fragility fractures. Baseline 24-hr urine calcium was 331 ±65 mg/day. Average exposure to denosumab therapy was 9.0 ± 4.8 doses. 27 of these patients received concomitant thiazide diuretics during the course of their denosumab therapy. Baseline t-scores were -2.4 ± 0.8 at lumbar spine, -1.5 ± 0.7 at total hip and -1.8 ± 0.5 at femoral neck. After denosumab therapy, the t-scores were respectively -1.9 ± 0.9, -1.3 ± 0.8 and -1.6 ± 0.7. Mean increases in BMD were seen at the lumbar spine of 6.2 ± 8.4%, at the total hip of 3.2 ± 6.0%, and at the femoral neck of 2.5 ± 8.0% 19 patients were considered to have (+) BMD responses, based on consistent increases in BMD and/or t-scores across all spine and hip sites. 4 patients had (-) BMD responses, based on decreased BMD and/or t-scores across all sites. 6 patients had mixed responses and 2 did not have comparative BMD data. Baseline urine calcium did not seem to correlate with clinical responses. Those patients with longer duration of thiazide and/or denosumab use had higher likelihood of (+) BMD responses. However, during the course of follow-up, 4 subjects suffered 7 fragility fractures while treated with denosumab: 3 with (+) and 1 with (-) BMD responses. Conclusion: Denosumab can effectively increase BMD in a cohort of osteoporosis patients with IHC, the majority of whom also received thiazide. However, increased BMD response did not necessarily predict lower risks of fragility fractures. Further research needs to evaluate the role of denosumab therapy in such high-risk patients.
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