[Osteogenon in therapy of distal radial bone fractures in patients with secondary osteoporosis].

AIM: To assess efficacy of osteogenon in consolidation of solitary fractures of distal part of the radial bone (RB) in patients with secondary osteoporosis (SO) due to rheumatoid arthritis (RA) and chronic renal failure (CRF). MATERIAL AND METHODS: The study group consisted of 7 patients with documented RA and 8 patients with CRF caused by chronic glomerulonephritis or chronic pyelonephritis in the predialysis period. The control group comprised 13 patients (6 and 7 patients, respectively). The patients were matched by clinico-demographic and therapy characteristics. Patients of the study group received osteogen from the fracture diagnosis to its consolidation. RESULTS: Osteogenon has an analgetic effect, improves well being, raises physical activity, reduces duration of fracture consolidation in patients with SO.

Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study).

CONTEXT: In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy. OBJECTIVE: The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength. DESIGN: This was an open-label, randomized controlled trial. PARTICIPANTS AND METHODS: We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 µg sc daily, denosumab 60 mg sc every 6 months, or both. RESULTS: Total volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001). Cortical porosity at both the radius and tibia increased progressively over the 24-month treatment period in the teriparatide group but was stable in both other groups (P < .001 teriparatide vs both other groups). Trabecular vBMD at the tibia increased similarly in all groups, whereas radius trabecular vBMD increased more in the combination group than the other groups (P < .01 for both comparisons). Finite element analysis-estimated strength improved or was maintained by all treatments at both the radius and tibia. CONCLUSIONS: Two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone. These findings suggest that this regimen may be beneficial in postmenopausal osteoporosis.

Muscle atrophy and bone loss after 90 days' bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study.

Muscle atrophy and bone loss pose substantial problems for long-term space flight and in clinical immobilization. We therefore tested the efficacy of flywheel resistive exercise and pamidronate to counteract such losses. Twenty five young healthy males underwent strict bed rest with -6 degrees head-down tilt for 90 days. Subjects were randomized into an exercise group that practiced resistive exercise with a 'flywheel' (FW) device every 2-3 days, a pamidronate group (Pam) that received 60 mg pamidronate i.v. 14 days prior to bed rest and a control group (Ctrl) that received none of these countermeasures. During the study, Ca(++) and protein intake were controlled. Peripheral quantitative computed tomography (pQCT) was used to assess bone mineral content (BMC) and muscle cross sectional area (mCSA) of calf and forearm. Measurements were taken twice during baseline data collection, after 28 and after 89 days bed rest, and after 14 days recovery. On the same days, urinary Pyridinoline excretion and serum levels of alkaline phosphatase, Ca(++) and PTH were measured. Pre-study exercise habits were assessed through the Freiburg questionnaire. Losses in calf mCSA were significantly reduced in FW (Ctrl: -25.6% +/- 2.5% Pam: -25.6% +/- 3.7%, FW: -17.3% +/- 2.7%), but not in the forearm mCSA (Ctrl: -6.4% +/- 4.33%, Pam: -7.7% +/- 4.1%, FW: -7.6% +/- 3.3%). Both diaphyseal and epiphyseal BMC losses of the tibia were mitigated in Pam and FW as compared to Ctrl, although this was significant only at the diaphysis. Inter-individual variability was significantly greater for changes in BMC than in mCSA, and correlation of BMC losses was poor among different locations of the tibia. A significant positive correlation was found between change in tibia epiphyseal BMC and serum cortisol levels. These findings suggest that both countermeasures are only partly effective to preserve BMC (FW and Pam) and mCSA (FW) of the lower leg during bed rest. The partial efficacy of flywheel exercise as well as the bones' response to unloading per se underlines the importance of mechanical stimuli. The huge variability of BMC changes, however, suggests that other factors affect changes in whole-bone strength following acute mechanical disuse.

A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial.

CONTEXT: One in 4 men in the United States aged >50 years will have an osteoporosis-related fracture. Fewer data are available on osteoporosis treatment in men than in women. OBJECTIVE: The purpose of this study was to evaluate denosumab therapy in men with low bone mineral density (BMD). DESIGN: This was a phase 3 study with 2 treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. SETTING: This was a multicenter study conducted in North America and Europe. PARTICIPANTS: A total of 228 men entered the open-label phase and 219 completed the study. INTERVENTION: Men from the original denosumab (long-term) and placebo (crossover) groups received 60 mg of denosumab sc every 6 months. MAIN OUTCOME MEASURES: BMD, serum collagen type I C-telopeptide, and safety were measured. RESULTS: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine, 0.9% total hip, 1.3% femoral neck, 1.3% trochanter, and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P < .01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to those of the long-term denosumab group during the first treatment year. Significant reductions in serum collagen type I C-teleopeptide were observed after denosumab administration. Adverse event rates were similar between groups, and no new safety signals were identified. CONCLUSIONS: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and in men with prostate cancer receiving androgen deprivation therapy.

Calcium supplementation and bone loss: a review of controlled clinical trials.

The responsiveness of postmenopausal women to supplementation with calcium appears to depend on their menopausal age. In women who are within the first 5 y of menopause, bone loss from the radius is attenuated but not arrested by added calcium. The maximal effect appears to occur with supplement dosages of approximately 1000 mg elemental Ca/d. In contrast, the spine is unresponsive to supplementation with calcium even at higher doses in early postmenopausal women. In late postmenopausal women, bone loss from the radius is attenuated by increased calcium intake. Loss from the spine can be retarded by increasing calcium intake to the current recommended dietary allowance in older women with low usual calcium diets. The effect of supplementation with higher doses of calcium in this segment of the population is unknown. Finally, the effect of added calcium on hip density of postmenopausal women is not yet established.

An analysis of bone regeneration at a segmental bone defect by controlled release of bone morphogenetic protein 2 from a biodegradable sponge composed of gelatin and ß-tricalcium phosphate.

To treat large bone defects is a clinically challenging problem and utilizing tissue engineering technology is an attractive approach for overcoming such a problem. Previously, a biodegradable sponge incorporating bone morphogenic protein-2 (BMP-2), which can control the release of BMP-2 for a prolonged time in an in vivo environment, was reported. In addition, a biodegradable sponge composed of gelatin and ß-tricalcium phosphate (ßTCP), gelatin-ßTCP sponge to develop a more ideal scaffold for enhancing bone regeneration was also created and previously reported. The purpose of this study was to investigate the effectiveness of the gelatin-ßTCP sponge for the promotion of bone regeneration in a critical-sized bone defect site in vivo. Apparent bone regeneration was induced by the gelatin sponge incorporating BMP-2 and the gelatin-ßTCP sponge with BMP-2 incorporation. In contrast, no apparent bone formation was induced by either the gelatin sponge only or the gelatin-ßTCP sponge without BMP-2. To investigate the quality of the regenerated bone, we conducted a biomechanical evaluation with a three-point bending test. We found no significant difference between the gelatin sponge incorporating BMP-2 and the gelatin-ßTCP sponge incorporating BMP-2 groups. Incorporation of ßTCP into the gelatin sponge was expected to enhance biomechanical strength during the initial bone regeneration. However, our observations showed that the gelatin-ßTCP sponge did not significantly improve the quality of regenerated bone from the viewpoint of biomechanical assessment, even though it did not impair the effectiveness of the promotion of bone regeneration by BMP-2 in the bone defect.

Iatrogenic osteomalacia in epileptic children. A controlled therapeutic trial.

Bone mineral content (BMC) ub tge forearms (related to total body calcium) was measured for a controlled therapeutic trial in 25 epileptic children on long-term treatment with phenytoin and in 22 normal children before and during treatment with vitamin D or placebo. In the epileptic children, hypocalcaemia and elevated serum alkaline phosphatase was found in 20% and 16%, respectively. The group of epileptic children treated with vitamin D2 (2000 IU daily) for 3 months showed a significant increase in bone mineral content, 5% on average. The epileptic children treated with placebo showed a significant decrease, 2% on average, while the normal children treated with vitamin D or placebo showed no change in bone mineral content. The results indicate a possible benefit of prophylactic vitamin D treatment in epileptic children.