Association of polymorphism at the type I collagen (COL1A1) locus with reduced bone mineral density, increased fracture risk, and increased collagen turnover.
(1/578)
OBJECTIVE: To examine the relationship between a common polymorphism within intron 1 of the COL1A1 gene and osteoporosis in a nested case-control study. METHODS: We studied 185 healthy women (mean +/- SD age 54.3+/-4.6 years). Bone mineral density (BMD) was measured using dual x-ray absorptiometry, and fractures were determined radiographically. The COL1A1 genotype was assessed using the polymerase chain reaction and Bal I endonuclease digestion. RESULTS: Genotype frequencies were similar to those previously observed and in Hardy-Weinberg equilibrium: SS 61.1%, Ss 36.2%, and ss 2.7%. Carriage of at least one copy of the "s" allele was associated with a significant reduction in lumbar spine BMD (P = 0.02) and an increased risk of total fracture (P = 0.04). Urinary pyridinoline levels were significantly elevated in those with the risk allele (P < 0.05). CONCLUSION: These data support the findings that the COL1A1 gene polymorphism is associated with low BMD and fracture risk, and suggest a possible physiologic effect on total body turnover of type I collagen. (+info)
Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving long term corticosteroid treatment. A double blind, randomised placebo controlled study.
(2/578)
OBJECTIVE: To study the effect of cyclic etidronate in secondary prevention of corticosteroid induced osteoporosis. METHODS: A double blind, randomised placebo controlled study comparing cyclic etidronate and placebo during two years in 37 postmenopausal women receiving long term corticosteroid treatment, mainly for polymyalgia rheumatica (40% of the patients) and rheumatoid arthritis (30%). Bone density was measured in the lumbar spine, femoral neck, and femoral trochanter. RESULTS: After two years of treatment there was a significant difference between the groups in mean per cent change from baseline in bone density in the spine in favour of etidronate (p = 0.003). The estimated treatment difference (mean (SD)) was 9.3 (2.1)%. Etidronate increased bone density in the spine (4.9 (2.1)%, p < 0.05) whereas the placebo group lost bone (-2.4 (1.6)%). At the femoral neck there was an estimated difference of 5.3 (2.6)% between the groups (etidronate: 3.6% (1.4)%, p < 0.05, placebo: -2.4 (2.1)%). The estimated difference at the trochanter was 8.2 (3.0) (etidronate: 9.0 (1.5)%, p < 0.0001, placebo: 0.5 (2.3)%). No significant bone loss occurred in the hip in placebo treated patients. CONCLUSIONS: Cyclic etidronate is an effective treatment for postmenopausal women receiving corticosteroid treatment and is well tolerated. (+info)
Vitamin D receptor alleles predict growth and bone density in girls.
(3/578)
OBJECTIVES: Polymorphism of the vitamin D receptor (VDR), collagen alpha I type I (Col I alpha I), and oestrogen receptor (ER) genes have been shown to account for some of the heritability of bone mineral density (BMD) in adults. This study examined this relation in prepubertal children. METHODS AND SUBJECTS: The relation between genotypes of VDR gene (Taq I, Bsm I, Fok I), Col I alpha I gene (Msc I), and ER gene (Pvu II) with areal BMD, volumetric BMD, and growth were examined in 114 (68 girls) healthy 7 year old, white children. RESULTS: The genotype of the VDR gene (Taq I) correlated with lumbar spine (L1-4) volumetric BMD in girls only, but at no other bone sites. In girls, VDR genotype affected areal BMD at all sites. After adjusting for height and weight, however, this effect was explained completely by the independent effect of the VDR genotype on growth. Girls with genotype TT, were 3.9 kg heavier and 4.1 cm taller than those with tt, but this relation was not present at birth. No relation was found between genotypes of the VDR gene (Fok I), Col I alpha I gene (Msc I), or ER gene (Pvu II) and BMD or growth variables. CONCLUSIONS: In prepubertal girls, VDR alleles contribute to lumbar spine volumetric BMD variance, but the areal BMD effect reflects the relation between areal BMD and growth. VDR alleles might affect postnatal growth regulation. (+info)
Effects of single and concurrent intermittent administration of human PTH (1-34) and incadronate on cancellous and cortical bone of femoral neck in ovariectomized rats.
(4/578)
The purpose of this study is to determine the efficacy of concurrent treatment with human parathyroid hormone, hPTH (1-34), and bisphosphonate (incadronate) in augmenting cortical and cancellous bone mass of femoral neck in ovariectomized (OVX) rats. Forty-eight 11-week-old female Sprague-Dawley rats were divided into eight groups (six animals in each group). The baseline control group was killed at the beginning of the experiment, at 11 weeks of age. An ovariectomy was performed in thirty rats and twelve rats were subjected to a sham surgery. OVX rats were untreated for the first four weeks of postsurgery to allow for the development of moderate osteopenia. These animals were then subjected to various treatments with either PTH, incadronate, or PTH+ incadronate for a period of 4 weeks. Right proximal femora (femoral necks) were used for bone histomorphometry. After OVX 8 weeks, there was a significant decrease in cancellous bone mass and cortical bone area of femoral neck in the OVX rats when compared to the sham control rats. In OVX rats treated with PTH alone or PTH+ incadronate were completely restored lost cancellous and cortical bone mass of femoral neck by increase bone formation. The bone formation parameters (OS/ BS, MS/BS) and bone turnover (BFR/BV) seen with PTH plus incadronate were similar to those seen with PTH treatment alone. This indicates that incadronate did not blunt the anabolic action of PTH when used concurrently. Our results suggest the followings: 1) the femoral neck of OVX rats is a suitable sample site for preclinical studies of the prevention of bone loss induced by estrogen depletion; 2) concurrent use of incadronate did not blunt the anabolic effect of PTH; 3) concurrent treatment showed the best results in restoring cancellous and cortical bone mass; and 4) it had additional benefits for bone strength independent of that achieved by the increase in bone mass. (+info)
Reduced bone density at completion of chemotherapy for a malignancy.
(5/578)
OBJECTIVES: Osteoporosis and pathological fractures occur occasionally in children with malignancies. This study was performed to determine the degree of osteopenia in children with a malignancy at completion of chemotherapy. METHODS: Lumbar spine (L2-L4) bone mineral density (BMD; g/cm2) and femoral neck BMD were measured by dual energy x ray absorptiometry in 22 children with acute lymphoblastic leukaemia (ALL), and in 26 children with other malignancies. Apparent volumetric density was calculated to minimise the effect of bone size on BMD. Results were compared with those of 113 healthy controls and expressed as age and sex standardised mean Z scores. RESULTS: Patients with ALL had significantly reduced lumbar volumetric (-0.77) and femoral areal and volumetric BMDs (-1.02 and -0.98, respectively). In patients with other malignancies, femoral areal and apparent volumetric BMDs were significantly decreased (-0.70 and -0.78, respectively). CONCLUSIONS: The results demonstrate that children with a malignancy are at risk of developing osteopenia. A follow up of BMD after the completion of chemotherapy should facilitate the identification of patients who might be left with impaired development of peak bone mass, and who require specific interventions to prevent any further decrease in their skeletal mass and to preserve their BMD. (+info)
One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density.
(6/578)
BACKGROUND: Inhaled corticosteroids are recognised as the most effective agents in the treatment of asthma. However, concerns have been expressed about the effects of high doses of inhaled corticosteroids on safety in relation to bone resorption and formation. This study measures the effects of two inhaled corticosteroids on bone markers and bone mineral density (BMD) over one year. METHODS: A one year randomised, prospective, open parallel study comparing inhaled fluticasone propionate (FP), 500 micrograms twice daily in 30 patients, and budesonide (BUD), 800 micrograms twice daily in 29 patients, delivered by metered dose inhaler and large volume spacers was performed in adults with moderate to severe asthma. Biochemical markers of bone turnover (osteocalcin, procollagen type 1 C-terminal propeptide (PICP), immunoreactive free deoxypyridinoline (iFDpd), N-terminal crosslinked telopeptides of type I collagen (NTx)), BMD at the spine and femoral neck, and serum cortisol concentrations were measured at baseline and 12 months later. RESULTS: There were no significant differences between the inhaled steroids on bone markers of bone resorption and formation or bone mineral density. Bone mineral density of the spine increased slightly in both groups over the 12 month period. Serum osteocalcin levels increased from baseline in both treatment groups (FP 16.9%, p = 0.02; BUD 14.3%, p = 0.04). PICP did not differ significantly from baseline. Both markers of bone resorption (iFDpd, NTx) varied considerably with no significant changes after one year. There was a significant correlation in percentage change from baseline between BMD of the spine and osteocalcin at 12 months (r = 0.4, p = 0.017). Mean serum cortisol levels remained within the normal range in both groups following treatment. CONCLUSION: There was no evidence of a decrease in BMD during 12 months of treatment with high doses of either FP or BUD. The change in spine BMD correlated with the increase in osteocalcin. Studies extending over several years are needed to establish whether these findings persist. (+info)
Relationship between urinary pyridinium cross-links, disease activity and disease subsets of ankylosing spondylitis.
(7/578)
OBJECTIVE: In this study, we aimed to determine the urinary levels of pyridinium cross-links and urinary beta-isomerized fragments derived from the C-telopeptide of the alpha1 chain of type I collagen (beta-CTX) as markers of bone resorption in patients with ankylosing spondylitis (AS), and to study their relationship to markers of disease activity [erythrocyte sedimentation rate (ESR)] and to disease subsets of this condition. METHODS: The serum calcium, osteocalcin (OC), parathormone (PTH), 25 OHD3 levels, beta-CTX and the urinary combined free pyridinolines (f-Pyr + f-Dpyr), urinary free deoxypyridinoline (f-Dpyr) and urinary free pyridinoline (f-Pyr) were evaluated and compared in 32 AS patients and 25 controls. Bone mineral density (BMD) was evaluated at the lumbar spine and the femoral neck. RESULTS: The serum markers of bone metabolism (serum calcium, PTH, 25 OHD3 and OC) were in the normal range in the AS group. AS patients had a lowered lumbar spine BMD (P = 0.01) (corresponding T score: P = 0.03), but femoral neck BMD did not differ significantly between AS and controls (P = 0.08) (corresponding T score: P = 0.11). There was no difference in the urinary levels of pyridinium cross-links and beta-CTX between AS patients and controls. A positive correlation between ESR, (f-Pyr + f-Dpyr) (r = 0.42; P = 0.018) and f-Dpyr (r = 0.49; P = 0.005) was observed. In the different disease subsets of AS, we found that patients with peripheral involvement had higher (f-Pyr + f-Dpyr) (P = 0.04) and f-Dpyr levels (P = 0.04), patients with early disease had elevated (f-Pyr + f-Dpyr) (P = 0.01), f-Dpyr (P = 0.02) and f-Pyr (P = 0.01) levels, and that those with raised ESR had enhanced f-Dpyr (P = 0.009) excretion. Patients were then stratified according to disease duration, peripheral involvement and sex, and this allowed us to observe that only urinary f-Dpyr remained elevated in patients independently from these variables and that raised ESR is the more relevant parameter for explaining this high level of excretion. CONCLUSION: We conclude that there was no difference in the levels of urinary pyridinium cross-links and beta-CTX between AS and controls. However, urinary excretion of some of these collagen compounds was enhanced in subgroups of AS, mainly in patients with raised ESR. Thus, AS patients with laboratory evidence of active disease could have a higher risk of bone loss. (+info)
Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group.
(8/578)
OBJECTIVE: To investigate whether the incidence of vertebral fractures is related to the magnitude of change in bone mineral density (BMD) during alendronate treatment. METHODS: Women in this study were age 55-81 years (n = 2,984). While participating in the Fracture Intervention Trial, they received 5 mg/day of alendronate for 2 years followed by 10 mg/day for the remaining 12-30 months of the study. Their BMD was measured at baseline and at 12 and 24 months, and spine radiographs were obtained at baseline and again at 36 or 48 months to identify new vertebral fractures. RESULTS: After 12 months of alendronate treatment, 35% of participants had increases of > or =3% in total hip BMD, and 21% had either decreased total hip BMD or no change. Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period. Only 3.2% of women with increases of > or =3% in total hip BMD experienced new vertebral fractures, whereas twice as many women (6.3%) whose BMD declined or stayed the same experienced new fractures (adjusted odds ratio 0.45, 95% confidence interval 0.27-0.72). Similar patterns were observed for spine BMD at 12 months, and for both sites using change in BMD at 24 months. CONCLUSION: Women with increases of > or =3% in BMD during the first 1 or 2 years of alendronate treatment had the lowest incidence of new vertebral fractures. These findings suggest that, among women taking antiresorptive agents, greater increases in BMD are associated with lower risk of new vertebral fractures. (+info)