Bone
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Comparative Study
Effects of droloxifene on prevention of cancellous bone loss and bone turnover in the axial skeleton of aged, ovariectomized rats.
The purpose of this study was to determine the efficacy of droloxifene (DRO), an estrogen antagonist/agonist, in preventing ovariectomy (OVX)-induced lumbar vertebral cancellous bone loss and bone turnover in aged female rats. Fifty-three Sprague-Dawley female rats were OVX or sham-operated at 19 months of age, and divided into 6 groups: (I) sham-operated controls; (II) OVX vehicle controls; (III) OVX rats treated with E2 at 30 micrograms/kg/day; (IV)-(VI) OVX rats treated with DRO at either 2.5, 5, or 10 mg/kg p.o. daily. The treatment period was 8 weeks. ⋯ However, DRO had no effect on uterine weight at either 2.5 or 10 mg/kg/day, while it only slightly but significantly increased uterine weight over OVX controls at 5 mg/kg/day. We conclude that DRO was efficacious in the prevention of lumbar vertebral cancellous bone loss and in the decline of total serum cholesterol but had no effect on uterine weight in the aged, OVX female rats. Our data suggest that DRO is a potentially useful agent for the prevention of vertebral bone loss leading to spinal fractures in postmenopausal women.
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Randomized Controlled Trial Multicenter Study Clinical Trial
Effects of oral alendronate and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with osteoporosis.
The main objective of this study was to determine the effect of daily oral alendronate treatment on bone mass in postmenopausal women affected by osteoporosis. The efficacy of intranasal salmon calcitonin was also examined. Nine centers in Italy enrolled 286 postmenopausal women between the ages of 48 and 76 with spinal bone mineral density > or = 2 SD below adult mean peak in the two-year, double-blind, randomized, placebo-controlled trial. ⋯ In contrast, intranasal salmon calcitonin failed to increase bone mineral mass significantly at any site. Both alendronate doses significantly decreased serum alkaline phosphatase, serum osteocalcin, and urinary pyridinolines, markers of bone turnover, whereas placebo and intranasal calcitonin did not. Alendronate was generally well tolerated and no serious adverse events were attributed to its use.(ABSTRACT TRUNCATED AT 250 WORDS)
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The activity of a novel calcitonin SB 205614 was compared with salmon calcitonin (sCT) and (Asu1,7)-eel calcitonin (ELC) in six different models of osteoclastic bone resorption in vitro and in vivo. SB 205614 is an ELC analogue that has an acetylenic bridge instead of the natural disulphide bridge, rendering the molecule more stable biologically than sCT and equally stable to ELC. Our aim was to determine whether this structural change compromised biologic activity, and if not, whether the increased stability could be used to exploit novel modes of administration. ⋯ Maximal effects were similar, whereas in general the hypocalcemic effect of SB 205614 was of a longer duration than the other two calcitonins; this was reflected in a larger area over the curve (AOC). However, following IN administration in the rabbit, where an aerosol delivery device similar to that used in the clinic was used to administer the calcitonins, SB 205614 (100 IU/kg) induced a highly significant two-fold increase in the AOC compared to ELC or sCT. The calcitonins were also compared in assays designed to measure therapeutic efficacy in the rat.(ABSTRACT TRUNCATED AT 400 WORDS)
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The effect of clodronate on healing of the fracture of osteopenic bone was studied in rats. A total of 165 female rats (14 +/- 1 weeks, 216 +/- 2 g) were divided into five fracture groups (n = 30), and a neurectomized group (n = 15). Osteopenia (op) was induced by right sciatic neurectomy 4 weeks before the fracture. ⋯ Clodronate did not affect normal bone strength. In conclusion, clodronate did not affect the bending strength of op fracture nor the strength of the control bones. The remodeling of the fracture was delayed with clodronate.
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Comparative Study Clinical Trial
Marked decrease in trabecular bone quality after five years of sodium fluoride therapy--assessed by biomechanical testing of iliac crest bone biopsies in osteoporotic patients.
Sodium fluoride has for more than 2 decades been a commonly used therapeutic agent for established osteoporosis because of a repeatedly documented anabolic effect on trabecular bone mass. Recently, however, three controlled trials have failed to demonstrate any therapeutic advantage of NaF over placebo with respect to vertebral fracture rate. Also, there have been several reports of an increased incidence of nonvertebral fractures during fluoride administration. ⋯ After 1 year of treatment, no difference was observed in iliac crest trabecular bone ash content. A general trend for decreased bone strength and bone quality was observed, but this was insignificant. After 5 years of fluoride treatment, an insignificant decrease in iliac crest trabecular bone ash content was observed.(ABSTRACT TRUNCATED AT 250 WORDS)