Postmenopausal Osteoporotic Patients Research Articles

Effects of sodium fluoride, vitamin D, and calcium on cortical bone remodeling in osteoporotic patients

The purpose of this histomorphometric study of iliac bone biopsies from 10 postmenopausal osteoporotic patients was to describe the effects of sodium fluoride (combined with calcium and vitamin D) on remodeling in cortical bone after 6 months and after 5 years of treatment. Biopsies had been fixed in absolute methanol, embedded undecalcified in methylmetacrylate, and cut on a heavyduty microtome. The therapy had no effect on the thickness of cortical bone in the iliac crest but increased the porosity slightly. It had no statistically significant effect on depth of resorption or thickness of new walls formed at remodeling sites but treatment increased the fraction of osteons undergoing remodeling in cortical bone. After 6 months of treatment, the increase was due to an enhanced activation of new remodeling sites, but in biopsies taken after 5 years of treatment, some degree of mineralization defect was observed and the duration of the remodeling cycle appeared to be prolonged. The mechanism underlying this qualitative change in the response to treatment is unknown, and it is unclear whether the mineralization defect may be prevented by, e.g., an altered supplementation of vitamin D or calcium.

Effects of nandrolone decanoate therapy on bone mass and calcium metabolism in women with established post-menopausal osteoporosis: a double-blind placebo-controlled study

In many patients with involutional osteoporosis anabolic steroids may produce a rapid subjective improvement and a pronounced reduction in the frequency of complaints. Animal experiments have demonstrated that anabolic steroids can also have an objective effect on bone tissue. Twenty (20) post-menopausal osteoporotic patients were randomly assigned to 2 different treatment regimens; 10 patients were treated with 50 mg i.m. of nandrolone decanoate (ND) every 3 wk for 12 mth and 10 patients were treated with a placebo. Both groups also received an oral calcium supplement (1 g/day). Bone mineral content (BMC) was measured by dual photon absorptiometry before and after 1, 3, 6 and 12 mth of treatment. Plasma alkaline phosphatase (ALP) and urinary hydroxyproline excretion were measured at the same time. Intestinale calcium absorption was measured by the 47Ca oral test before and after treatment. A transiliac bone biopsy was performed before and after treatment in 4 patients in each group. After 1 yr there was a significant increase in lumbar spine BMC in the group receiving calcium plus ND. A progressive increase in plasma ALP was also observed in the group treated with ND but this was not significant, whereas radiocalcium absorption did increase significantly in this group. Histomorphometric study of bone samples demonstrated a significant increase in trabecular bone volume (TBV) and in active osteoid surface area in the patients treated with ND. Because plasma ALP tends to increase when a small decrease in bone resorption occurs (as measured by urinary hydroxyproline excretion) and the active osteoid surfaces also significantly augment, we concluded that ND therapy increases the bone formation rate through inhibition of bone resorption. This interpretation could explain the considerable increase in lumbar spine BMC and the significant increase in TBV observed in patients treated with ND.

The Role of Skeletal Calcium Deficiency in Postmenopausal Osteoporosis

BURNELL, JAMES M.; BAYLINK, DAVID J.; CHESNUT, CHARLES H. III; TEUBNER, ELIZABETH J. Author Information

Bone metabolism in rheumatoid arthritis compared with postmenopausal osteoporosis.

Calcium and bone metabolism in 29 rheumatoid arthritis (RA) patients were compared with those in 27 postmenopausal osteoporotic patients. Signs of vitamin D deficiency were found in 20 RA patients, including 12 who took recommended amounts of vitamin D in their diets and were exposed to sufficient sunlight, and in none of the osteoporotic patients. There were no signs of malabsorption. In six out of 15 patients we found increased liver enzyme activity, which may have a role in vitamin D metabolism. We propose the influence of non-steroidal anti-inflammatory drugs (NSAIDs) on vitamin D metabolism in the liver as a possible explanation.

Bone loss in premenopausal and postmenopausal women. A cross-sectional and longitudinal study using quantitative computed tomography.

Trabecular and total bone densities were determined by quantitative computed tomography in patients with untreated postmenopausal osteoporosis and in normal premenopausal and postmenopausal women. A special procedure was used for precise low-dose examinations of the distal end of the radius and the distal end of the tibia. The results indicate that the trabecular bone density of the peripheral skeleton is a reliable index of postmenopausal osteoporosis. In general, osteoporotic patients could be distinguished from patients with age-related bone loss based on differences in the magnitude of the decrease in trabecular bone density. Serial determinations of trabecular bone density in individual patients indicated that trabecular bone loss in postmenopausal osteoporotic patients shows a step-wise pattern in which phases of relative stability are followed by brief phases of bone loss. Quantitative computed-tomography measurements of bone density should provide a better understanding of the pathogenesis of postmenopausal osteoporosis and be useful in the assessment of different methods of treatment.

Expansion of the medullary cavity at the expense of cortex in postmenopausal osteoporosis

Transilial biopsies from postmenopausal osteoporotic patients showed that static features and remodeling activity tended tended to form a pattern, with the area midway between the cortices having less bone and lower remodeling activity than the area closer to the inner boundary of the cortex. The appearance, enlargement, and coalescence of the resorption cavities within the subendosteai area of the cortex lead to negative bone balance and a progressive trabeculation of the cortex, resulting in the formation of a transitional zone. Therefore, in most cases we can distinguish two different zones, transitional and trabecular zones, within the area usually known as the trabecular bone area. The transitional zone undergoes more active remodeling than the trabecular zone and has an important role in evaluation of the traditional trabecular bone volume and remodeling dynamics depending on the field selection for this evaluation, i.e., the proportion between transitional and trabecular zones within the selected fields. We postulate that the appearance of resorption cavities in the subendosteal area of the cortex depends on osteoclast work, and bone loss in the resulting transitional zone depends on a combination of excessive osteoclast work and defective osteoblast work, with the osteoclast excessive work predominating.

Improved method for quantitative determination in serum of alkaline phosphatase of skeletal origin.

In this quantitative method for detection of skeletal alkaline phosphatase (EC 3.1.3.1) activity in human serum, intestinal and placental alkaline phosphatase activities are recognized by their susceptibility to inhibition by L-phenylalanine, and skeletal and hepatic alkaline phosphatases are distinguished by their different sensitivities to inactivation by heat. Alkaline phosphatase isoenzymes prepared from organ sources may behave differently from the corresponding isoenzymes in serum. Our procedure allows us to include organ-derived internal standards of skeletal, intestinal, and biliary alkaline phosphatase to minimize between-assay variation. In preliminary applications, we have found that (a) total serum alkaline phosphatase activity is extremely variable in post-menopausal osteoporotic subjects and is not a reliable index of skeletal alkaline phosphatase activity; (b) seven osteoporotic patients responding to therapy with sodium fluoride with increased bone formation showed increased skeletal alkaline phosphatase activity in their serum as compared with age-matched controls (p less than 0.005); and (c) 10 post-menopausal osteoporotic patients responding to therapy with stanozolol with increased total body calcium showed an increase in circulating skeletal alkaline phosphatase activity (p less than 0.001).

Three-year changes in bone mineral mass of postmenopausal osteoporotic patients based on neutron activation analysis of the central third of the skeleton.

Thirty-two patients with postmenopausal osteoporosis have been followed for periods of 3 yr or more to assess the effects of treatment on bone mineral mass based on sequential measurements of bone mineral in the central third of the skeleton. Neutron activation analysis (NAA) was used to measure calcium in the trunk and proximal femurs. The NAA measurement is expressed as an index, CaBI, which relates the subject's Ca value to the estimated mean value for normal subjects of the same size based on height and arm span. Bone and serum fluoride concentrations were measured, and bone biopsies were carried out in many cases. The treatments consisted of various combinations of NaF (25 mg, twice daily), calcium (1 g/day), vitamin D2 (50,000 IU twice weekly), and estrogen (0.625 mg/day). NaF was always given in combination with Ca and vitamin D2. During the 3-yr treatment period, the 32 patients showed changes in bone mineral mass from losses of −10.5% to increases of 21%. The coefficient of variation of 9% for ch...

The vitamin D metabolites in the pathogenesis and management of osteoporosis.

Studies on post-menopausal osteoporotic patients indicate that 1,25-(OH)2 D3 concentrations are no different from those in age-matched normal subjects and the data suggest that the malabsorption of calcium found in many osteoporotic patients cannot generally be attributed to low plasma 1,25-(OH)2 D3 levels. The effects are discussed of three different therapies - sex hormones alone, vitamin D metabolites alone and a combination of both - on calcium balance and peripheral bone loss in treated compared with untreated osteoporotic patients. The results indicate that combined therapy with a vitamin D metabolite and an oestrogen is more effective in inhibiting the rate of bone resorption in post-menopausal osteoporosis than treatment with either agent used alone, and should be regarded as the treatment of choice at the present time. It is suggested that, using this regimen which is suitable for patients up to about 65 years of age, calcium supplementation is not required, provided daily calcium intake is reasonably adequate, and may even be undesirable by increasing the risk of hypercalcaemia.

Histological studies of bone from normocalcemic post-menopausal osteoporotic patients with increased circulating parathyroid hormone.

Quantitative histological evaluations were made of nondecalcified iliac crest needle biopsies were obtained from 16 untreated, normocalcemic, normophosphatemic postmenopausal osteopenic females. Six of the patients had elevated circulating immunoreactive parathyroid hormone. Morphometric parameters, which were significantly increased in the hyperparathyroid group compared with the euparathyroid patients were the cortical osteoclast count and the percentage of trabecular surface covered by active or inactive osteoid. In addition, in all patients, the cortical osteoclast count, and the per cent of trabecular surface covered by osteoid and inactive osteoid were directly related to levels of immunoreactive parathyroid hormone. These data suggest that progressive osteopenia in some patients with crush fracture, or postmenopausal or senile osteoporosis, may be conditioned by an osteoclastosis, elevations in circulating parathyroid hormone, and a relative increase in poorly mineralized osteoid tissue. As such they emphasize the heterogeneity of a so-called "osteoporotic population" and stress the need for specific histological morphometric evaluation of bone before initiating long-term therapeutic modalities.

Effect of single dose intravenous zoledronic acid on bone mineral density in post-menopausal osteoporosis of Bangladeshi women

The osteoporosis is a major health threat that affects every third post-menopausal women. Postmenopausal osteoporosis is complicated with vertebral, femoral or radius fracture. This prospective study on post-menopausal osteoporosis was carried out in the Pain Centre, Department of Anaesthesia, Analgesia and Intensive Care Medicine of BSMMU, Dhaka during the period of January 2008 to January 2010. The post-menopausal women with back pain were screened by spinal radiographs and dual-energy X-ray absorptiometry (DXA) of lumbar spine to determine the bone mineral density (BMD). The woman after menopause with a BMD T-score of -2.5 or less with or without evidence of vertebral fracture is considered as post-menopausal osteoporosis. A total of 55 post-menopausal osteoporotic patients were assigned to receive a single dose of IV infusion of zoledronic acid (5 mg) along with dietary calcium and vitamin-D. The spinal radiographs and dual-energy X-ray absorptiometry (DXA) were repeated in all the 55 patients at 12 months following zoledronic acid infusion. The mean BMD of lumbar spine increased significantly from pre-infusion value of 0.75695 g/cm2 to post-infusion of 0.80216 g/cm2. The T-score also increased from pre infusion value of -3.567 +/- 0.77 to -3.158 +/- 0.08 in 12 months following the infusion (P < 0.01). The increase is 5.026% higher than pre infusion values. The spinal radiographs taken before infusion of zoledronic acid, showed 14 fractures. There was no new fracture in any case during the 12 months study period. So, it can be concluded that once yearly IV infusion of zoledronic acid is associated with a significant increase in BMD and decrease in the risk of vertebral fracture.