Additive impact of alfacalcidol on bone mineral density and bone strength in alendronate treated postmenopausal women with reduced bone mass.

OBJECTIVES: Assessment of additive impact of alfacalcidol 1 µg daily (Alfa) on bone mineral density (BMD) and on bone strength in postmenopausal women treated with alendronate 70 mg weekly + 500 mg calcium daily. SUBJECTS AND METHODS: In a randomized, double-blind, placebo controlled study, 279 postmenopausal women with osteoporosis or osteopenia participated (intention to treat analysis [ITT]; aged 73.6∓4.7 years) and were treated with 70 mg alendronate (ALN) weekly and 500 mg calcium daily for 36 months. In addition, these patients received either 1 µg alfacalcidol (Alfa) or placebo (PLC) daily. BMD was measured with Dual-Energy-X-ray-Absorptiometry (DXA) at the lumbar spine and proximal femur and at forearm and tibia with peripheral quantitative computed tomography (pQCT) at regular intervals for 36 months. RESULTS: DXA-BMD of lumbar spine (L1-4) increased after 36 months, by 6.65% (p<0.0001) in the Alfa/ALN group versus 4.17% (p<0.0001) in the PLC/ALN group. Group difference was significant after 3 years (p=0.026). At the end of the study, significant differences were found in favor of the Alfa/ALN group in trabecular density (tibia) (p=0.002), cortical density (midshaft tibia) (p=0.043), and bone strength (p=0.001). The remaining parameters showed no differences between the treatment arms, apart cortical bone density at midshaft radius. CONCLUSIONS: Alfacalcidol significantly increases the efficacy of alendronate treatment in osteopenic/osteoporotic postmenopausal women on spinal DXA-BMD, cortical and trabecular BMD of the tibia and also bending stiffness of the tibia.

Common musculoskeletal adverse effects of oral treatment with once weekly alendronate and risedronate in patients with osteoporosis and ways for their prevention.

OBJECTIVE: To examine in a major cohort of patients whether or not musculoskeletal adverse effects (MAEs), similar to those seen in intravenous bisphosphonates (BP), might occur also in high dosage oral treatment regimens with alendronate (ALN) and risedronate (RSN). PATIENTS AND METHODS: 612 consecutive patients treated in the osteoporosis outpatient clinic at Charite, Campus Benjamin Franklin, between July 2002 and October 2003 with oral ALN or RSN (mean age 68.2+/-9.7 years; 527 females, 85 males), were examined and followed up for MAEs. RESULTS: The overall frequency of any severe MAEs in our patients was low (5.6%). All severe MAEs occurred in primarily once weekly treated patients: 27 in ALN 70 mg once weekly (27/134=20.1%) and 7 in RSN 35 mg once weekly (7/28=25.0%), with no significant difference between those groups. The most frequently reported MAE was acute arthralgia in 12.6%, followed by acute back pain in 9.1% of all primarily once weekly treated cases. None of the 302 patients initially treated with daily BP reported any MAEs when later switching to once weekly administration (218 patients to ALN 70 mg once weekly and 84 patients to RSN 35 mg once weekly). With reference to recently published data, the phenomenon is probably related to dose dependent gammadelta T cell activation by accumulation of isopentenyl pyrophosphate (IPP) due to inhibition of the mevalonate pathway by nitrogen containing bisphosphonates (nBP). CONCLUSIONS: MAEs in oral BP are, in general, less common and severe than in intravenous BP. They are observed exclusively in patients starting ALN or RSN treatment with once weekly dosage regimens. In order to avoid this phenomenon, it is suggested to start ALN or RSN treatment with the lower daily dosages of ALN 10 mg daily or RSN 5 mg daily for about two weeks before switching to the overall, more convenient, once weekly dose regimen.