Bone Mineral Density Turnover Research Articles

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys

This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30mg/kg) or alendronate (0.5mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis.

Bone mineral density and turnover in children with attention-deficit hyperactivity disorder receiving methylphenidate.

Attention-deficit hyperactivity disorder (ADHD) is the most common behavior disorder among children; methylphenidate is a drug frequently prescribed for the control of its symptoms. One of the potential side effects of methylphenidate that concerns parents is its impact on the growth of children, since the mechanism by which methylphenidate might influence growth is not known. As linear growth is associated with an increase in bone mineral density and turnover, this study was undertaken to evaluate bone mineral density by dual photon absorptiometry and bone turnover by measuring serum bone-specific alkaline phosphatase and the urinary deoxypyridinoline excretion rate in children treated with methylphenidate for 1 to 2 years as compared to a control group. There were no significant differences in bone mineral density at either the lumbar spine or femoral neck in the study group (0.662 +/- 0.04 and 0.735 +/- 0.07 g/cm2, respectively) as compared to the controls (0.675 +/- 0.05 g/cm2 and 0.734 +/- 0.07 g/cm2, respectively). Furthermore, there were no significant differences in serum bone-specific alkaline phosphatase in the study group (58 +/- 22 U/L) as compared to the control children (71 +/- 34 U/L) or in urinary deoxypyridinoline in the study group (34 +/- 38 nM/mM), as compared to the control group (27 +/- 12 nM/mM). In conclusion, our data do not support a significant effect of methylphenidate on bone mineral density turnover in children when used for 1 to 2 years.