Men's Osteoporosis Support GroupOnce-yearly IV zoledronic acid bone effects J Bone Miner Res. 2008 Jan;23(1):6-16. Effects of intravenous zoledronic Acid once yearly on bone remodeling and bone structure. Recker RR and others. PMID: 17892374. This is a complex study which used various microscopic methods to check the bone health of patients who had been treated with a single 5 mg IV dose of zoledronic acid (Reclast) each year for a total of three years. All patients were women with a total of 147 biopsy cores (79 on active treatment and 68 on placebo) from the iliac crest used. The authors stated: "In conclusion, 3 yr of treatment with intravenous zoledronic acid 5 mg once yearly yielded a significant 63% median reduction in bone turnover, resulting in significant decreases in surface undergoing active remodeling and preservation of bone architecture. Moreover, zoledronic acid increased osteoblastic MAR (mineral apposition rate). No evidence for adverse effects on bone safety in the form of excessive reduction of bone turnover, woven bone formation, or osteomalacia were demonstrable in patients treated with zoledronic acid." In short, although the rate of bone resorption was reduced by zoledronic acid, there was adequate bone formation with no evidence of abnormal bone formation. Editor's comments: Reclast is FDA approved for postmenopausal women and presumably could be used off-label for men. It would be enticing to think of only once-yearly injections as opposed to weekly oral medications. This would mainly be a consideration in individuals with G.I. problems that might affect absorption of oral bisphosphonates with the IV route totally bypassing the potential problem area. This study shows that bone health is good on the microscopic level after three years of Reclast use. This study showed a mean 71% reduction in bone turnover as indicated by the term activation frequency (Ac.f). One interesting note is that the authors refer to another study by Chavassieux PM, and others in 1997 which showed that 10-mg/day Fosamax (alendronate) caused a 92% reduction in Ac.f. after two years on medication. This was a near complete reduction in bone turnover rate. In view of the recent Update on bisphosphonate-induced osteonecrosis of the jaws (BIONJ), the very high reduction in bone turnover caused by Fosamax may explain the great percentage of cases of BIONJ related to that medication in the Marx and others study. It is pure conjecture, but the daily dose of Fosamax might contribute to greater reductions in bone turnover, never giving periods without drug intake to perhaps allow the turnover rate to increase gradually. There were, however, only two cases in the Marx and others study where the patients were on daily Fosamax dosing, so other dosing regimens can also decrease bone turnover enough to lead to BIONJ. Note that Reclast was given in a single 5-mg dose per year. When it is given for malignant conditions, under the name Zometa, it is given in 4-mg doses every 3-4 weeks.
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