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The aim of this study was to determine whether clodronate reduced the incidence of vertebral fractures in patients with osteoporosis. We report here the interim analysis after 1 year of a 3-year double-blind placebo-controlled study. The objectives of the interim analysis were to determine whether there was a trend in fracture frequency and to examine the effects of clodronate on bone mineral density...
Hyperphosphatemic tumoral calcinosis (HTC) is an inherited metabolic disorder characterized by calcified soft tissue masses and hyperphosphatemia. Besides these typical features, a number of less common manifestations have been reported, all of them related to pathologic calcification of various tissues. We have investigated the case of a woman with hyperphosphatemia, recurrent episodes of lumbar...
The effects of coffee on bone metabolism are still controversial, although several studies have suggested that caffeine and/or heavy coffee consumption is associated with a significant increase in risk of fracture, osteoporosis, and periodontal disease. Therefore, we sought to clarify the relationship between coffee consumption and bone metabolism using male Wistar rats. Forty-eight male Wistar rats...
In an effort to elucidate the role of mechanical stimuli in rheumatoid arthritis, we determined mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and three transcription factors (c-fos, ets-1, and ets-2) under two mechanical shearing conditions as well as simulated unloading. Human synovial cell cultures (MH7A and RA99-01), derived...
Intermittently administered parathyroid hormone (PTH) is a potent bone anabolic agent. We aimed to determine the impact of long-term treatment with PTH on bone structure, dynamics, and mineralization. We ovariectomized (ovx) 1-year-old rats with the exception of a baseline and a sham-operated group. Twelve weeks later, a 36 week treatment with PTH analog SDZ PTS 893 (12.5, 25, 50, 100 μg/kg), human...
Prostaglandins E (especially PGE 2 ) stimulate bone formation and increase bone mass in several species including man. The mechanism for this effect, the target cells, and the receptors involved are not known. Specific cell-surface receptors for PGE 2 (EP 1-4 ) have been cloned and characterized. EP 4 was reported to be the major receptor in embryonic and...
The purpose of this cross-sectional study was to evaluate the effects of human parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17β-estradiol (E 2 ), risedronate (Ris), or a reduced dose of hPTH (LowPTH) on cortical bone in the ovariectomized (ovx) rat. Eight groups of ovx and one group of intact female rats (3.5 months) were left untreated for 11 weeks. For the following...
Aging is associated with gradual bone loss in men and premenopausal women, with an accelerated rate of loss after menopause in women. Although many studies have investigated bone loss due to surgically induced estrogen depletion, little is known regarding normal age-related changes in bone mass in animal models. We used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD),...
Porous collagen disks (6 mm diameter, 1 mm thickness) were impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 μg/disk) and implanted onto the back muscles of mice. Pentoxifylline (PTX), which is a methylxanthine-derived inhibitor of phosphodiesterases (PDEs), or vehicle, was injected (5, 25, 50, 100, 200, and 300 mg/kg body weight/day) into the mice subcutaneously once a...
The hormonal actions of 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] are mediated by its cognate receptor protein, the vitamin D receptor (VDR). Despite the growing importance of the VDR system as a modulator of cell growth and differentiation, convenient assays for quantitative measurement of VDR are not readily available, and [ 3 H]1,25(OH) 2 D 3 ligand...
This prospective study evaluated bone loss in the peri- and postmenopausal period in 156 women followed from age 48 to 64 years. All women were premenopausal at the start of the study. Areal bone mineral density (g/cm 2 ) was measured by single-photon absorptiometry (SPA) of the forearm at the 1 cm level (BMD 1 cm) and the 6 cm level (BMD 6 cm) every second year. Onset of menopause (MP) was...
Macrophage-colony stimulating factor (M-CSF) is an essential requirement for human osteoclast formation, but its effect on the proliferation and differentiation of circulating osteoclast precursor cells is unknown. Other growth factors and cytokines are also known to support/stimulate osteoclast formation from mouse marrow precursors, but it is not certain whether these factors similarly influence...
Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis,...
Cathepsin K (cat K) is the major cysteine protease expressed in osteoclasts and is thought to play a key role in matrix degradation during bone resorption. However, little is known regarding the synthesis, activation, or turnover of the endogenous enzyme in osteoclasts. In this study, we show that mature cat K protein and enzyme activity are localized within osteoclasts. Pulse-chase experiments revealed...
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