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Biomedical subjects

D Dempster

Publications and source records attributed to D Dempster.

7 recordsLinked to original sources

[Effects of 1 alpha(OH)D3 on trabecular and cortical bone in ovariectomized rats].

OBJECTIVE: To study the pharmaceutical effects of 1 alpha(OH)D3 on trabecular and cortical bone in ovariectomized (OVX) rats. METHODS: 41 female Wistar rats of six months old were randomly divided into 5 groups: (1) Baseline control; (2) Sham control; (3) 6 weeks after OVX (OVXb); (4) 14 weeks after OVX (OVXe); (5) OVX + 0.1 microgram/(kg.d) 1 alpha(OH)D3 (O + VD), treatment started 6 weeks after OVX and lasted 8 weeks. Histomorphometry analysis of tibia, peripheral quantitative computed tomography (pQCT) scanning of femur, bone biomechanical test and serum and urinary biochemical parameters were determined. RESULTS: The levels of bone turnover indexes increased in OVX rats, OVX also resulted in reducing of trabecular, bone mass and biomechanical properties. The ratio of urinary deoxypyridinoline crosslink/creatinine was decreased by 67.0% in O + VD group compared with OVXe group 67.0% [(43.50 +/- 11.20) nmol.L-1/mmol.L-1 vs(131.80 +/- 14.90) nmol.L-1/mmol.L-1, P < 0.01]. Percent trabecular area (Cn-BV/TV) was increased by 89.8% in O + VD group compared with OVXe group (11.03 +/- 0.73 vs 5.81 +/- 1.29, P < 0.05). Trabecular bone mineral content and density were increased by 77.3% and 91.3% compared with OVXe respectively (P < 0.05). Although cancellous maximal load and stiffness increased in O + VD group, but no statistical significance. 1 alpha(OH)D3 also enhanced polar moment of inertia (PMI) and maximal load of cortical bone in femur compared with OVXe (23.70 +/- 1.63 vs 18.23 +/- 1.41, P < 0.01 and 171.69 +/- 9.92 vs 147.58 +/- 11.29, P < 0.05 respectively). CONCLUSION: 1 alpha(OH)D3 inhibited the higher bone turnover induced by OVX, increased trabecular bone in proximal tibia and bone mass in distal femur. 1 alpha(OH)D3 also improved the mechanical properties of cortical bone in femur.

Animals↗

Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis.

BACKGROUND: Small increases in bone mass are commonly seen with existing treatments for osteoporosis, which reduce bone remodelling and primarily prevent bone loss. Since these drugs reduce but do not eliminate risk of fractures, an anabolic agent that would increase bone mass and potentially cure the underlying skeletal problem is needed. METHODS: We did a 3-year randomised controlled trial to find out the effects of 1-34 human parathyroid hormone (hPTH [1-34], 400 U/25 micrograms daily subcutaneously) in postmenopausal women with osteoporosis taking hormone-replacement therapy (n = 17). The controls were women taking hormone-replacement therapy only (n = 17). The primary outcome was bone-mineral density of the lumbar vertebrae, with bone-mineral density at other sites and vertebral fractures as secondary endpoints. FINDINGS: Patients taking hormone-replacement therapy and PTH (1-34) had continuous increase in vertebral bone-mineral density during the 3 years, whereas there was no significant change in the control group. The total increase in vertebral bone-mineral density was 13.0% (p < 0.001); 2.7% at the hip (p = 0.05); and 8.0% in total-body bone mineral (p = 0.002). No loss of bone mass was found at any skeletal site. Increased bone mass was associated with a reduction in the rate of vertebral fractures, which was significant when fractures were taken as a 15% reduction in vertebral height (p = 0.04). During the first 6 months of treatment, serum osteocalcin concentration, which reflects bone formation, increased by more than 55%, whereas excretion of crosslinked n-telopeptide, which reflects bone resorption, increased by only 20%, which suggests some uncoupling of bone formation and resorption. By 6 months, there were similar increases in both markers, which gradually returned towards baseline as the study progressed. Vertebral bone-mineral density increased most during the first year of PTH treatment. INTERPRETATION: We found that PTH has a pronouned anabolic effect on the central skeleton in patients on hormone-replacement therapy. PTH also increases total-body bone mineral, with no detrimental effects at any skeletal site. The increased vertebral mass was associated with a reduced rate of vertebral fracture, despite increased bone turnover. Bone-mass changes may be consistent with a reduction in all osteoporotic fractures. If confirmed in larger studies, these data have important implications for the treatment of postmenopausal osteoporosis.

Absorptiometry, Photon↗

Insulin-like growth factor-I in men with idiopathic osteoporosis.

The etiology of osteoporosis in most men without a history of alcohol abuse, hypogonadism, or glucocorticoid excess is unknown. Several histomorphometric reports have demonstrated a reduction in indices of bone formation. We tested the hypothesis that the putative reduction in bone formation in men with idiopathic osteoporosis may be related to deficiencies in skeletal mechanisms that are mediated by insulin-like growth factor I (IGF-I). Twenty-four middle-aged men (50.5 +/- 1.9 yr) with severe idiopathic osteoporosis (mean lumbar spine T-score -3.5 +/- 0.16) were studied. The following biochemical indices were all normal: serum calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, testosterone, osteocalcin, carboxyterminal propeptide of type I collagen, bone specific alkaline phosphatase, urinary calcium, and collagen crosslinks. Parathyroid hormone level was in the lower range of normal, 25 +/- 2 pg/mL (nl: 10-65). Mean serum IGF-I level was also in the lower range of normal, 157.9 +/- 7.6 ng/mL (normal age-matched range, 140-260 ng/mL). Eight men had IGF-I levels that were below 140 ng/mL. The mean IGF-IZ score was -0.75, significantly different from the expected mean of zero (P = 0.0002). IGF-I was correlated negatively with age (r = -0.49, P < 0.02). With age held constant, serum IGF-I accounted for 15% of the variance in lumbar bone mineral density (BMD; P < 0.001). The osteocalcin concentration correlated well with bone density at the distal 1/3 radius (r = +0.44; P < 0.002). Histomorphometric analysis of bone biopsy specimens showed significant reductions in cancellous bone volume (31%; P < 0.001), cortical width (28%; P < 0.05), osteoid surface (33%; P < 0.01), and bone formation rate (54%; P < 0.01) when results were compared with age-matched control subjects. Percent eroded surface was normal and was correlated inversely with serum IGF-I levels (r = -0.5; P < 0.04). These results suggest that serum IGF-I levels are reduced in men with idiopathic osteoporosis and that IGF-I correlates with and may contribute to the reduction in lumbar spine bone mass density (BMD). The low IGF-I levels may reflect the reduction in bone formation demonstrated by histomorphometry. Insights into the etiology of idiopathic osteoporosis in men may be revealed by further studies of the IGF-I axis.

Adult↗

Hereditary hyperphosphatasia: 20 year follow-up and response to disodium etidronate.

We provide a 20 year follow-up of a family with three siblings affected by hereditary hyperphosphatasia (HH). An iliac crest bone biopsy was performed on one of the siblings following double-tetracycline labeling, with results reported quantitatively in a standard histomorphometric format. Biochemical parameters of disease activity were monitored in the patient before and after treatment with oral etidronate disodium, 20 mg/kg/day taken for 5 weeks. Biochemical evidence of intense disease activity continued 20 years after the initial diagnosis of HH in the sibling studied. His bone biopsy specimen also revealed extremely high bone turnover but low cancellous bone volume and osteoclasts unlike those found in Paget's disease. Treatment with etidronate disodium resulted in a temporary 40% reduction in serum alkaline phosphatase and 24 h urine hydroxyproline excretion, with reduction in serum osteocalcin from two times the upper limit of normal to a subnormal level. We conclude that disease activity in HH can continue unabated for two decades. Our bone biopsy finding of low cancellous bone volume, the consistent lack of pagetic-looking osteoclasts in our and other studies, plus the clinical features of HH (childhood onset and extremely diffuse disease with gross skeletal deformation) serve to distinguish HH from Paget's disease. Bisphosphonates may be of value in treating HH.

Adult↗

Dual-photon Gd-153 absorptiometry of bone.

Dual-photon absorptiometry with gadolinium 153 was used to measure the mineral content of lumbar vertebrae in cadavers, excised vertebrae with marrow, and dry, marrow-free vertebrae. The error introduced by the surrounding soft tissue of cadavers was 3%, and the error in determining mineral mass or density in excised vertebrae was about 5%. The correlation coefficient between the results of Gd-153 and corrected iodine 125 (single-photon) absorptiometry on 24 femoral necks was 0.99, and the predictive error was 3.7%. Dual-photon absorptiometry accurately indicates bone mass and bone density and is only slightly affected by either surrounding tissue or fat changes in bone marrow.

Bone Marrow↗

Total hip replacement of failed surface arthroplasty.

Twelve patients who underwent 13 revisions were followed for a mean of 3 years. There were no complications. In addition, in all patients, the results of the total hip replacements were similar to, or better than, the results of the surface replacements prior to their failure. A previous surface replacement does not appear to prejudice the outcome of a total hip replacement.

Aged↗