ORIGINAL ARTICLE Bisphosphonates in children with hypercalciuria and reduced bone mineral density Michael Freundlich & Uri S. Alon Received: 15 March 2008 / Revised: 5 May 2008 / Accepted: 9 June 2008 / Published online: 13 August 2008 # IPNA 2008 Abstract 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 parathy- roid hormone remained normal as well. In summary, in children with IH and decreased BMD, treatment with bisphosphonates normalized urine calcium excretion, elim- inated 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. Keywords Bisphosphonates . Bone mineral density . Bone resorption . Calciuria . Osteopenia Introduction The etiology of idiopathic hypercalciuria (IH) remains unknown in many cases. The consensus, though, is that the IH might be due either to increased calcium (Ca) absorption from the gut, increased losses in the kidney, increased bone resorption, or any combination of the above [1, 2]. In the majority of children with IH, including those with stones, treatment is prescribed without further inves- tigation into the source of the hypercalciuria. Treatment includes high fluid intake, dietary modification, and the use of potassium (K) citrate preparations and thiazide diuretics [3]. Whereas treatment is effective in most patients, a minority of children continue to display persistent hyper- calciuria. In adults, the association of hypercalciuria with osteo- penia is well established [4–7]. In those with severe osteopenia, Jaeger et al. [8] found significantly higher incidence of fractures. In children, Garcia-Nieto et al. [9] found 30% of the 72 hypercalciuric children investigated to have decreased bone mineral density (BMD). The associ- ation of hypercalciuria or hypercalciuric stone disease with osteopenia in children was confirmed by Freundlich et al. Pediatr Nephrol (2008) 23:2215–2220 DOI 10.1007/s00467-008-0940-9 M. Freundlich Pediatric Nephrology, University of Miami, Miami, FL, USA U. S. Alon Bone and Mineral Disorders Clinic, Section of Pediatric Nephrology, Children’ s Mercy Hospital and Clinics, University of Missouri–Kansas City, School of Medicine, Kansas City, MO, USA U. S. Alon (*) Pediatric Nephrology, Childrens Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA e-mail: ualon@cmh.edu