Bisphosphonates in children with hypercalciuria and reduced bone mineral density

Previous studies have demonstrated reduced bone mineral density (BMD) and biochemical changes of excessive bone resorption in some patients with idiopathic hypercalciuria (IH). Consequently, bisphosphonates have been successfully employed in research animals and adults with IH and reduced BMD. We evaluated the effect of treatment with bisphosphonates in seven patients ages 10-16 years with persistent IH and reduced BMD. In five children, preceding traditional therapy failed. All children received oral alendronate and one also IV Zoledronic acid for 6-18 (median 9.0, mean 10.7) months. With treatment, BMD Z scores in the lumbar spine improved from -2.0 +/- 0.3 to -0.8 +/- 0.8 (p = 0.002) and in the femoral neck from -1.8 +/- 0.4 to -0.7 +/- 0.9 (p = 0.01); urine N-telopeptides/creatinine decreased from 372 +/- 289 to 72 +/- 39 nmol/mmol (p = 0.05) and calcium/creatinine from 0.29 +/- 0.12 to 0.13 +/- 0.06 mg/mg (p = 0.009). Height Z scores, normal at baseline in all, remained unaffected, and no new stones or fractures were documented throughout the treatment period. Serum creatinine, electrolytes, calcium, phosphorus and parathyroid hormone remained normal as well. In summary, in children with IH and decreased BMD, treatment with bisphosphonates normalized urine calcium excretion, eliminated urinary symptoms, and significantly improved reduced BMD. These short-term beneficial effects indicate the need for larger prospective studies on the potential of bisphosphonates to serve as a new tool in treating children with IH and reduced BMD.