Calcified tissue international
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Calcif. Tissue Int. · Apr 2003
Long-term zoledronic acid treatment increases bone structure and mechanical strength of long bones of ovariectomized adult rats.
Zoledronic acid (ZOL) is a highly potent heterocyclic bisphosphonate which has been shown to inhibit bone resorption in short-term experiments in young growing animals. In this investigation we have evaluated the effects of a 1-year administration to mature, ovariectomized (OVX) rats as a model for postmenopausal osteoporosis in order to elucidate (1) the temporal changes in urinary biochemical markers of bone turnover and femoral bone mineral density (BMD), (2) to measure changes of static and dynamic histomorphometric parameters and mechanical strength, and (3) to assess the preventive effects of chronic treatment with ZOL on these parameters. In urine, deoxypyridinoline increased after OVX and was significantly reduced by ZOL administration, indicative of a reduced bone collagen turnover. ⋯ Multiregression analysis revealed a significant positive correlation between maximum load and BMD, and a significant negative correlation of maximum load with labeled perimeter, a marker of bone formation and turnover. No significant correlation was found with urinary deoxypyridinoline, a marker of bone resorption. The data show that mechanical testing detects improvements of functional bone quality following low dose bisphosphonate treatment which are not identified by standard DXA measurements of BMD.
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Calcif. Tissue Int. · Dec 2002
Randomized Controlled Trial Clinical TrialRandomized, double-blind, clinically controlled trial of intranasal calcitonin treatment in patients with hip fracture.
The objective of this study was to evaluate the short-term outcome of intranasal calcitonin treatment of elderly hip fracture patients on pain, bone loss, functional recovery, and length of hospital stay. In addition, we wanted to compare the effect of calcitonin with placebo on fusion of hip fractures treated with internal fixation using a screw or a nail. In a randomized, double-blind, clinically controlled trial, 260 independently living patients (aged 65 years or older) with acute hip fracture were randomly assigned to intranasal calcitonin 200 IU daily for 3 months or matching placebo nasal spray. ⋯ There were no significant differences in mortality, side effects, length of hospital stay, and functional recovery. Among patients with internal fixation using a screw or a nail (n = 99), fusion of the fracture was observed in an X-ray 3 months after the operation in 84% in the calcitonin group and in 63% in the placebo group (P = 0.029, difference 20% [95% CI 2 to 39]). We conclude that intranasal calcitonin might be useful for hip fracture patients but the clinical significance of this finding needs to be confirmed by studies with more participants, a longer treatment period, a longer follow-up, and perhaps a higher dose of calcitonin.
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Calcif. Tissue Int. · Jan 2002
The first stage of transforming growth factor beta1 activation is release of the large latent complex from the extracellular matrix of growth plate chondrocytes by matrix vesicle stromelysin-1 (MMP-3).
Transforming growth factor beta-1 (TGF-beta1) is secreted in a biologically inactive form and stored in the extracellular matrix as a 290 kDa complex consisting of the mature TGF-beta1 homodimer (Mr 25 kDa), the latency-associated peptide (LAP; Mr 75 kDa), and the latent TGF-beta1 binding protein-1 (LTBP1; Mr 190 kDa). Latent TGF-beta1, composed of these three components, is known as the "large latent TGF-beta1 complex." In contrast, latent TGF-beta1 without LTBP1 is known as "small latent TGF-beta1." For all latent forms, dissociation of the TGF-beta1 homodimer from LAP is necessary for growth factor activation and acquisition of biological activity. Matrix vesicles produced by growth plate chondrocytes contain matrix metalloproteinases that can activate small latent TGF-beta1. ⋯ Further, the data suggest that release of the large complex occurs via cleavage at several novel sites in the 130 kDa LTBP1 molecule. Since matrix vesicle MMP-3 is also able to activate small latent TGF-beta1, these results suggest that the large latent TGF-beta1 complex protects against activation of the small latent TGF-beta1. Thus, the data suggest that release of the large latent TGF-bl complex from the matrix and activation of the latent growth factor are only two steps of what must be at least a three-step process.
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Calcif. Tissue Int. · Oct 2001
Randomized Controlled Trial Clinical TrialRisedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy.
Limited information is available on the effect of bisphosphonates in men receiving corticosteroid therapy. We studied 184 men among the patients enrolled in two, double-blind, placebo-controlled, 1-year studies with similar protocols. The studies evaluated the effects of risedronate in patients beginning corticosteroid treatment at a dose of at least 7.5 mg per day of prednisone or equivalent (prevention study) or continuing long-term treatment of corticosteroid at that dose (treatment study). ⋯ When the data from the two studies were combined, the incidence of vertebral fractures decreased 82.4% (95% confidence interval, 36.6%-95.1%) in the pooled risedronate groups compared with placebo (P = 0.008). Risedronate was well tolerated in men, with a similar incidence of upper gastrointestinal adverse events in the placebo and treatment groups. Daily treatment with risedronate increases bone density and decreases vertebral fracture risk within 1 year in men receiving corticosteroid therapy.