Intermittent and continuous administration of the bisphosphonate ibandronate in ovariohysterectomized beagle dogs: Effects on bone morphometry and mineral properties

Bisphosphonates have emerged as a valuable treatment for postmenopausal ost eoporosis. Bisphosphonate treatment is usually accompanied by a 3-6% gain i n bone mineral density (BMD) during the first year of treatment and by a de crease in bone turnover. Despite low bone turnover, BMD continues to increa se slowly beyond the first year of treatment. There is evidence that bispho sphonates not only increase bone volume but also enhance secondary minerali zation, The present study was conducted to address this issue and to compar e the effects of continuous and intermittent bisphosphonate therapy on stat ic and dynamic parameters of bone structure, formation, and resorption and on mineral properties of bone. Sixty dogs were ovariohysterectomized (OHX) and 10 animals were sham-operated (Sham), Four months after surgery, OHX do gs were divided in six groups (n = 10 each). They received for 1 year iband ronate daily (5 out of 7 days) at a dose of 0, 0.8, 1.2, 4.1, and 14 mu g/k g/day or intermittently (65 mu g/kg/day, 2 weeks on, 11 weeks off). Sham do gs received vehicle daily. At month 4, there was a significant decrease in bone volume in OHX animals (p < 0.05), Doses of ibandronate greater than or equal to 4.1 mu g/kg/day stopped or completely reversed bone loss. Bone tu rnover (activation frequency) was significantly depressed in OHX dogs given ibandronate at the dose of 14 mu g/kg/day, This was accompanied by signifi cantly higher crystal size, a higher mineral-to-matrix ratio, and a more un iformly mineralized bone matrix than in control dogs. This finding lends su pport to the hypothesis that an increase in secondary mineralization plays a role in gain in BMD associated with bisphosphonate treatment. Moreover, i ntermittent and continuous therapies had a similar effect on bone volume. H owever, intermittent therapy was more sparing on bone turnover and bone min eral properties. Intermittent therapy could therefore represent an attracti ve alternative approach to continuous therapy.