Long-term Oral Bisphosphonate Research Articles

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

Bisphosphonates decrease bone resorption and are commonly used to treat or prevent osteoporosis. However, the effect of bisphosphonates on their target cells remains enigmatic, since in patients benefiting from therapy, little change, if any, has been observed in the number of osteoclasts, which are the cells responsible for bone resorption. We examined 51 bone-biopsy specimens obtained after a 3-year, double-blind, randomized, placebo-controlled, dose-ranging trial of oral alendronate to prevent bone resorption among healthy postmenopausal women 40 through 59 years of age. The patients were assigned to one of five groups: those receiving placebo for 3 years; alendronate at a dose of 1, 5, or 10 mg per day for 3 years; or alendronate at a dose of 20 mg per day for 2 years, followed by placebo for 1 year. Formalin-fixed, undecalcified planar sections were assessed by bone histomorphometric methods. The number of osteoclasts was increased by a factor of 2.6 in patients receiving 10 mg of alendronate per day for 3 years as compared with the placebo group (P<0.01). Moreover, the number of osteoclasts increased as the cumulative dose of the drug increased (r=0.50, P<0.001). Twenty-seven percent of these osteoclasts were giant cells with pyknotic nuclei that were adjacent to superficial resorption cavities. Furthermore, giant, hypernucleated, detached osteoclasts with 20 to 40 nuclei were found after alendronate treatment had been discontinued for 1 year. Of these large cells, 20 to 37% were apoptotic, according to both their morphologic features and positive findings from in situ end labeling. Long-term alendronate treatment is associated with an increase in the number of osteoclasts, which include distinctive giant, hypernucleated, detached osteoclasts that are undergoing protracted apoptosis.

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

Giant Osteoclast Formation and Long-Term Oral Bisphosphonate Therapy

Potential excessive suppression of bone turnover with long-term oral bisphosphonates therapy in postmenopausal osteoporotic patients (prospective study monitored with biochemical marker of bone turnover)

Potential excessive suppression of bone turnover with long-term oral bisphosphonates therapy in postmenopausal osteoporotic patients (prospective study monitored with biochemical marker of bone turnover)

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, χ2). 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.

Jaw osteonecrosis in patients treated with bisphosphonates: MDCT evaluation

This study was done to evaluate the use of multidetector computed tomography (MDCT) in the evaluation of jaw osteonecrosis, a recently described medical entity in patients receiving long-term intravenous or oral bisphosphonates, and to help radiologists recognise it to enable early diagnosis and appropriate management. Thirty-eight patients with a history of neoplasm (breast, prostate, multiple myeloma, pancreas) or osteoporosis and bisphosphonate use and recent oral surgery who presented with pain in the mouth and temporomandibular joints, soft tissue infections, altered taste and numbness were examined with MDCT. In all patients, MDCT revealed the presence of structural bony alterations referable to osteonecrosis associated with orosinusal fistula in four of them and bony intraoral spicules in 25. Jaw osteonecrosis is an established medical entity discovered in patients who have undergone treatment with bisphosphonates and dental extraction or other oral surgery. MDCT with multiplanar (MPR), volume rendering (VR) and three-dimensional (3D) reconstructions allows accurate assessment of affected bone structures, enabling early diagnosis and suitable treatment planning. Radiologists should be aware of the risk of osteonecrosis in patients treated with bisphosphonates and be able to distinguish it from other bone diseases (osteomyelitis and osteoradionecrosis) with which it enters the differential diagnosis.

Effect of Long‐Term Oral Bisphosphonates on Implant Wound Healing: Literature Review and a Case Report

Bisphosphonates suppress osteoclast activity, and their intravenous use has been reported in hundreds of cases to be associated with osteonecrosis in the jaw. Little is known of the risks associated with long-term use of oral bisphosphonates despite their use for >10 years by an oral mode of delivery for the treatment of osteopenia, osteoporosis, and Paget's disease of bone. The purpose of this report is to review the literature associated with bisphosphonate use that could impact bone healing and to report a case of bone necrosis in a patient on long-term oral bisphosphonates. A Medline search was carried out to find relevant articles from both medical and dental literature between 1960 and 2006. A patient, who had been taking an oral bisphosphonate for >10 years, developed unexplained clinical signs of bone necrosis after routine dental implant placement. This case was followed, documented, and the treatment of the osteonecrosis described. A summary of how bisphosphonates may play a role in wound healing is presented. The compromised healing noted in a patient, who was under long-term oral bisphosphonate use, was successfully treated with systemic antibiotics, local microbial mouthrinse, and aggressive defect management (detoxification and mixture of bone graft and tetracycline). This case suggests that patients under long-term oral bisphosphonate use should be treated with caution. Well-controlled, prospective clinical trials on the effect of oral bisphosphonates on bone are warranted to determine which patients may be at risk for such complications.