Potential excessive suppression of bone turnover with long-term oral bisphosphonate therapy in postmenopausal osteoporotic patients

BACKGROUND: Bisphosphonates decrease bone resorption and bone formation. The excessive and prolonged suppression of bone turnover results in poor bone quality in the treatment of osteoporosis, although the relevant pharmacological benefits of bisphosphonates are widely known. Concerns have been raised about potential excessive suppression of bone turnover during long-term use. Bisphosphonates carry the potential risk of excessively suppressing bone turnover which can impair some of the biomechanical properties of bone, although they are reported to be generally safe and effective. OBJECTIVES: The aim of this study was to clarify the effects of long-term oral therapy with bisphosphonates on bone resorption and also on bone formation, using the bone markers urine cross-linked N-telopeptides of type 1 collagen (u-NTx) and bone-specific alkaline phosphatase. PATIENTS AND METHODS: Eighty-four Japanese postmenopausal patients were enrolled in this study. All patients were treated with oral bisphosphonates once a day before breakfast. Medication was continued for 24 months unless adverse events occurred. Alendronate was randomly prescribed for 41 patients and risedronate were prescribed for 43 patients. The u-NTx was measured at baseline, and at 6, 12, 18 and 24 months, using morning second-void urine samples. At the 24th month, laboratory assessment was carried out on each patient who had continued the oral bisphosphonate therapy for all the 24 months. RESULTS: Excessively low levels of u-NTx (<10 nmol BCE/mmol creatinine) were observed in four of the 84 patients (4.8%). Values of bone-specific alkaline phosphatase less than the standard range were observed in 9.4% (5/53 patients) at the 24-month follow-up (4/23 patients on alendronates and 1/30 patients on risedronate; p < 0.1, chi(2)). There was a trend in the occurrence of the lower deviation in patients receiving alendronate from the standard range of bone-specific alkaline phosphatase. CONCLUSION: Clinicians prescribing long-term bisphosphonate therapy should be aware of, and monitor for, the potential development of excessive suppression, not only in bone resorption but also in bone formation.