Established Osteoporosis Research Articles

6 Hormone replacement therapy for established osteoporosis in elderly women

6 Hormone replacement therapy for established osteoporosis in elderly women

Non-linear increase in vertebral density induced by a synthetic steroid (Org OD 14) in women with established osteoporosis

The results of a 2-year placebo-controlled study in 38 female patients with osteoporosis are presented. This study was conducted to evaluate the efficacy of a daily oral dose of 2.5 mg Org OD 14 ((7α,17α)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) in the treatment of established osteoporosis. Org OD 14 is a steroid which shows combined weak oestrogenic, androgenic and progestational activity. A total of 31 patients completed a 12-month study period (17 placebo. 14 Org OD 14) and 25 of these went on to complete the full 24-months (15 placebo, 10 Org OD 14). A significant increase in bone mineral density as measured by dual photon absorptiometry was recorded in the lumbar spine in the Org OD 14-treated patients at 8, 16 and 24 months. The gain in bone mass after 8 months averaged 4% ( P < 0.01) and after 24 months 8% ( P < 0.001). In the control group, a bone loss rate of 2% per year was recorded in the lumbar spine. No significant changes in bone density in the forearm as assessed by single photon absorptiometry were found in either group. The increase in spinal bone density in the Org OD 14 group was non-linear and followed an S-shaped upward pattern. Org OD 14, while inducing no appreciable endometrial stimulation, was found to be a bone-active compound with anti-resorbing as well as anabolic activity. Org OD 14 warrants consideration not only for the long-term prevention of bone loss but also for curative treatment of post-menopausal osteoporosis.

90318000 17β-Estradiol and continuous norethisterone: A unique treatment for established osteoporosis in elderly women

90318000 17β-Estradiol and continuous norethisterone: A unique treatment for established osteoporosis in elderly women

The Prevention of Osteoporosis

Osteoporosis is the most common metabolic bone disorder in the United States. The spine is frequently involved, so that elderly women with kyphosis due to multiple compression fractures ("dowager's hump") are commonly seen in a geriatric practice. However, the most serious manifestations of osteoporosis is hip fracture. Whereas vertebral crush fractures are painful and cause spinal deformity, hip fractures cause significant morbidity and mortality. Some 250,000 hip fractures occur each year in the United States, with a mortality of 12% to 20%. For those who survive the acute event, nearly half have their life-style dramatically changed. Many become chair-bound. Some need to enter nursing homes. Many become so despondent that they lose their will to live. The direct and indirect cost of caring for these patients is +7 billion to +12 billion a year. In the absence of adequate treatment of established osteoporosis, prevention takes on heightened importance. Several strategies require consideration, from dietary measures to hormonal treatments to the newest possibility, bisphosphonate therapy.

Fluoride treatment in osteoporosis

The use of fluoride for the treatment of established vertebral osteoporosis in adults with the symptomatic crush fracture syndrome is approved for use in 8 European countries.' This treatment was suggested by the low prevalence of osteoporosis in some areas where the drinking water contained moderately high concentrations of fluoride` and by the enormously increased bone density characteristic of fluorosis.5 There now exists a wealth of evidence and some controversy regarding the use of fluoride, and this article addresses the main issues involved.

Long-term treatment of established osteoporosis with intranasal calcitonin

We examined the long-term effects of intranasal administration of salmon calcitonin on bone and calcium metabolism in women with established osteoporosis (forearm fracture). Over a period of 5 years, 14 women received discontinuous calcitonin (200 IU) plus calcium (500 mg) daily for 3 years or 4 years. To allow assessment of the optimum duration of therapy, patients in whom treatment had been for shorter intervals were also included. At the end of the first 2 years, a group receiving placebo had lost significantly more bone from their spines and forearms than the group receiving calcitonin in the first year (P less than 0.01). In the 14 women who completed a further 3 years on calcitonin, the bone mineral contents of the spines increased continually. Bone loss in the forearm was arrested for 1 year. Treatment lasting for about 2 years prevented bone loss in both areas. Treatment for 3 years resulted in net gains in spinal bone but no further benefits in relation to forearms. Biochemical parameters of bone turnover (serum alkaline phosphatase levels, plasma bone Gla protein levels, and fasting urinary hydroxyproline/creatinine levels) exhibited similar declines irrespective of the duration of treatment. It is concluded that long-term intranasal treatment with calcitonin produced net gains in spinal bone and that optimum response in forearms was achieved using discontinuous therapy. The ratio between periods with and without treatment was between 1:2 and 2:3.

Toward a cure for osteoporosis: Reversal of excessive bone fragility

While estrogen replacement therapy and calcium supplementation appear to be effective at preventing postmenopausal osteoporosis, therapy for established osteoporosis is far less effective. The reduction of bone fragility should be a goal of a treatment for established osteoporosis. To this end, increases in cortical bone mass by subperiosteal new bone formation may produce the greatest mechanical advantage. Anti-resorptive drugs, such as etidronate, have shown potential for reducing the incidence of osteoporotic fracture in the short term, but their ability to produce a long-term benefit may be limited. An alternative approach might be to develop drug therapies that substantially increase cortical bone strength, namely by stimulating periosteal bone formation. Although sodium fluoride has proved to be problematic, there are several other potential osteoporosis therapies. They include treatment with anabolic hormones (e.g. growth hormone and anabolic steroids) and targeted delivery of growth factors. Also, anti-resorptive and formation-stimulating drugs might be combined in a new form of ADFR (coherence) therapy where the new acronym means: Activate-Depress-Formation stimulation-Repeat.

17β-Estradiol and Continuous Norethisterone: A Unique Treatment for Established Osteoporosis in Elderly Women

Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily. In the group treated with hormones bone mineral density in the spine (dual photon absorptiometry) and bone mineral content in the ultradistal forearm (single photon absorptiometry) increased highly significantly by 8-10% during the 1 yr of treatment. Bone mineral content in the mid-shaft of the forearm (single photon absorptiometry) and the total body bone mineral (dual photon absorptiometry) increased by 3-5% when compared to that in the placebo group, which showed virtually unchanged values at all measurement sites. Seven of the women treated with hormones were examined after a further year of treatment. BMC increased by another 3-6%, reaching a 12% increase in bone mineral density in the spine after 2 yr of treatment. Biochemical estimates of bone resorption (fasting urinary calcium and hydroxyproline) and bone formation (serum alkaline phosphatase and plasma osteocalcin), decreased significantly (P less than 0.001) in the group treated with hormones, but remained unchanged in the placebo group. The reduction in indices of bone resorption was more pronounced than that in bone formation after one year, indicating a positive bone balance. No further changes were seen in these bone turnover parameters during the second year of treatment. In the group treated with hormones, serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol decreased by about 12% (P less than 0.05-P less than 0.01), whereas high density lipoprotein cholesterol decreased by about 8% (P less than 0.001). The high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio was unchanged. The hormone treatment did not produce any major side effects, and only minor bleedings were experienced by a few women. The present study demonstrates that treatment with female sex hormones in this particular combination is a realistic approach to the treatment of women with established postmenopausal osteoporosis.

Discontinuous calcitonin treatment of established osteoporosis—effects of withdrawal of treatment

purpose: The purpose of this study was to examine the effects of discontinuous treatments with intranasal salmon calcitonin on bone and calcium metabolism in postmenopasal women and to establish the effects of withdrawing treatment.patients and methods: This report presents data from 26 postmenopausal women with established osteoporosis (forearms fracture) 12 months after withdrawal of a 1-year double-blind, placebo-controlled therapy with intranasal calcitonin. The women then resumed treatment with calcitonin 200 IU plus calcium 500 mg daily in an open design for an additional 1-year period. A control group of 19 age-matched women (no forearms fracture) did not receive any treatment.results: At the end of the 3 years, the control group had lost significantly more bone in the forearm (single photon absorptiometry) and spine (dual photon absorptiometry) than had the group treated with intranasal calcitonin for 2 years, whereas the group receiving calcitonin for 1 year had intermediate values. During the year of withdrawal, the rate of bone loss was similar in the women who had received calcitonin and those who had received placebo. Calcitonin was especially effective in women with initially high bone turnover and low bone mass. The bone response in the spine could, furthermore, be estimated by the changes in bone turnover.conclusion: Discontinuous treatment with intranasal calcitonin affects bone and calcium metabolism in established osteoporosis. In women with high-turnover osteoporosis, therapy results in a net gain of bone in both the peripheral and axial skeleton. Response to treatment may be monitored by changes in bone turnover.

Calcium supplementation of the diet: justified by present evidence.

BrMedJ 1990;300:1056-60 In a recent review Kanis and Passmore concluded that there was no case for supplementation of the diet with calcium for the prevention or treatment of osteoporosis.1 We consider that present evidence, taken as a whole, points to a different conclusion. We consider the matter under five main headings: experimental calcium deficiency; human calcium requirements; the relation between calcium intake, bone mass, and bone loss; the relation between calcium and hip fracture; and the role of calcium in established osteoporosis.

New Osteoporosis Therapies Appear Closer

PROGRESS toward the development of new therapies for osteoporosis was reported at the Second International Conference on Research Advances in Osteoporosis, in Arlington, Va, sponsored by the National Osteoporosis Foundation, the American Society for Bone and Mineral Research, and the National Institutes of Health. Among the treatments showing promise in clinical trials are diphosphonates and a nasal-spray form of calcitonin. Preliminary findings from a yet unpublished study, suggesting that a new, combined hormone therapy may actually increase spinal bone density in osteoporotic women, also were reported. While calcitonin-salmon (Calcimar, manufactured by Rorer Pharmaceuticals, Fort Washington, Pa) is currently approved for the treatment of established osteoporosis where estrogen is contraindicated, it is not used for prevention because it requires regular injections. In a controlled study conducted by Claus Christiansen, MD, Glostrup (Denmark) Hospital, involving 37 women with established postmenopausal osteoporosis, a new, nasal-spray form of the drug has been shown to

Low-dose calcitriol versus calcium in established postmenopausal osteoporosis

An ongoing randomized clinical trial of 3 years duration is being undertaken to evaluate the recurrent fracture rate and safety profile associated with low-dose cacitriol versus calcium supplementation in women with at least 3 years postmenopausal osteoporosis who are under the age of 80 years. A total of 856 patients were submitted for possible inclusion in the study by 123 primary care physicians, and 636 met all entry requirements. Each patient was randomly allocated to receive either 0.25 μg of calcitriol twice daily or calcium supplementation of 1,000 mg/d. If significant hypercalcemia developed (>2.6 mmol/L) or a deterioration in renal function was observed, the dose of trial medication was to be halved or stopped if laboratory values did not return to normal. Patients were given no specific instructions regarding dietary calcium intake. To date, 528 patient-years experience with calcitriol and 527 patient-years experience with calcium the calcium supplementation have been accumulated. Thus far, low-dose calcitriol has not been observed to cause hypercalcemia, deterioration in renal function, or nephrocalcinosis. At 1 year, a loss in total anterior height ( P < .05) has been detected in the calcium-treated group compared with the calcitriol-treated group. Thus, calcitriol appears to preserve spinal height. Long-term follow-up of all patients for 2 or 3 years will be continued.

Nasal calcitonin for treatment of established osteoporosis : Clin. Endocrinol.; 30/4 (435–442)/1989/

Nasal calcitonin for treatment of established osteoporosis : Clin. Endocrinol.; 30/4 (435–442)/1989/

Fluoride and osteoporosis.

ConclusionThere is substantial evidence that fluoride could play a major role in the treatment of established osteoporosis. If properly applied, this treatment could augment vertebral bone mass and inhibit fractures.However, certain problems of fluoride therapy have limited its wider applicability or acceptance. First, it has a very narrow therapeutic window. Thus, it has been difficult to maintain blood fluoride level above the therapeutic threshold without exceeding the toxic threshold. Second, fluoride treatment has been associated with frequent gastrointestinal and rheumatic complications, approximating 24 and 29%, respectively. Third, fluoride treatment may cause the formation of a mechanically defective bone. Fourth, fluoride may be toxic on osteoblasts at high concentrations. Thus, the beneficial effect of fluoride may be self-limiting. Finally, 25–30% of patients may not respond to fluoride.It is our conviction that these limitations of fluoride therapy may be largely overcome by the intermittent ...

Pathogenesis, prevention, and treatment of osteoporosis.

Many risk factors that predispose to osteoporosis have been identified, but the fundamental pathogenesis remains unknown. Abnormalities in systemic calcium regulating hormones are probably less important than changes in local factors. Risk factor analysis, particularly using bone mass measurements, can provide the basis for effective prevention programs with calcium, exercise, and hormone replacement therapy. Treatment of established osteoporosis is limited. In addition to a preventive regimen, further bone loss may be prevented by fluoride therapy, which stimulates bone formation, or calcitonin, which inhibits bone resorption.

2 Uses and limitations of bone biopsy in management of metabolic bone disease

Bone biopsy is now an established diagnostic and investigative procedure which is widely used in the management of metabolic bone diseases. Its unique feature is that it facilitates direct visualization of bone cells and bone structure and, through double tetracycline labelling, allows the indirect measurement of bone turnover. Its main diagnostic contribution has been in unravelling the complexities of renal osteodystrophy, which consequently is now much better understood. However, it has also uncovered a variety of mineralization defects caused by agents such as fluoride, diphosphonates and aluminum that might otherwise have bone unsuspected clinically. Its main investigative roles have been to provide unique insight into the mechanisms of bone loss with age and in osteoporosis, and to assess the effects on bone and bone cells of potential therapeutic agents in established osteoporosis. This has been possible through the use of histomorphometry, which is used to quantify changes in bone volume and turnover as well as alterations in the microanatomical structure of bone that can reduce bone strength and increase the risk of fracture. Although most biopsies will continue to be taken for histomorphometry, recent studies have shown that specimens may be used to provide additional information such as quantitation and localization of elements within bone, and to provide bone cells for in vitro culture. It is likely that, in future, specimens will be taken from patients with various disorders so that the techniques of cell and molecular biology can be applied to harvested bone cells and thus provide a new dimension to our understanding of metabolic bone disease.

Reversibility of nontraumatic disuse osteoporosis during its active phase

The potential for the recovery of bone lost during the active phase of disuse osteoporosis, both in the diaphyseal compacta and metaphyseal spongiosa was tested in young adult and old Beagle dogs. Immobilization for up to 60 weeks was achieved by placing the forelimb in a spica cast and remobilization by removing it. Bone volume was estimated in the third metacarpus, radius, ulna and humerus at the mid-diaphysis and at the level of distal metaphyseal spongiosa in both forelimbs by radiography and histomorphometry. Measurements carried out on animals remobilized showed considerable recovery of the original bone loss. In both age groups, the residual deficits increased, however, with the duration of immobilization and were similar in the metaphyseal spongiosa and in the diaphyseal compacta. The old dogs which began the study with 10% less bone than the younger dogs, showed smaller proportional losses than the younger dogs but greater residual deficits, most evident in the diaphysis. In both age groups the distal, weight-bearing bones tended to show greater losses and also greater recovery both in diaphyseal compacta and the metaphyseal spongiosa. Thus, 28 weeks after cast removal following 32 weeks of immobilization the following findings were noted: In the third metacarpal diaphyseal compacta in the younger dogs, a 53.6% loss (mostly from the periosteal envelope) decreased to 16.3% (a 70% recovery) while in the older dogs a 37.6% loss (mostly from the endosteal envelope) decreased to 23% (a 40% recovery). In metacarpal metaphyseal spongiosa in young adult dogs, a 50% loss reduced to 16.8% (a 66% recovery) while in the older dogs a 47% loss reduced to 19% (a 60% recovery). These observations apply only to the effect of remobilization on recovery of bone loss incurred during the active phase of disuse osteoporosis. The same potential for recovery may not exist later in the inactive phase of established disuse osteoporosis. The permanent losses, however, could be prevented by appropriate measures taken during the active phase of osteoporosis.

Treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation. Dose response and duty cycle.

We determined the dose-response characteristics of a low-voltage, high-frequency, capacitively coupled electrical signal that reverses an established osteoporosis in a rat tibial model with sciatic neurectomy. The electrical signals were delivered by means of stainless-steel gel-coated electrodes. In the first part of the study, the shape (sine wave) and frequency (sixty kilohertz) of the signal were kept constant while the voltage was varied from 0.01 to ten volts, peak to peak. Control osteoporotic and sham osteoporotic animals showed a mean loss of tibial ash weight of 19 and 17 per cent, respectively, twenty-eight days after sciatic neurectomy plus twelve days of no treatment using sham electrodes. Rats that were subjected to 0.25, 0.50, 1.0, 2.5, and 5.0 volts, peak to peak, for twelve days beginning on the twenty-eighth day after sciatic neurectomy all showed mean losses of tibial ash weight that were significantly less than those of the controls. The rats that had a 0.5-volt peak-to-peak signal showed the least mean loss of tibial ash weight (only 6 per cent). We concluded that a capacitively coupled electrical signal, delivered through gel-coated electrodes, can largely reverse an established disuse osteoporosis due to neurectomy in the rat tibia. In the second part of the study, the duty cycles of a sine-wave, sixty-kilohertz, 0.5-volt peak-to-peak signal were varied (12.5, 50, and 100 per cent on), and the wet, dry, and ash weights were determined and compared with those of unstimulated osteoporotic controls. Only the 100 per cent duty-cycle signal was effective in reversing the loss of bone mass in the neurectomized tibiae.

Effects in postmenopausal women of natural and synthetic estrogens on calcitonin and calcium-regulating hormone secretion. Relevance to postmenopausal osteoporosis.

The major function of calcitonin in man appears to be the prevention of excessive or unwanted bone resorption. There is a marked sex difference in circulating levels, with a relative deficiency in women. As calcitonin secretion in young women is known to be increased by estrogens, long periods of estrogen lack - such as the postmenopause - are possibly associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of postmenopausal bone loss, especially as the latter is believed to be due to excessive bone resorption. We have studied the effects of three exogenous estrogens on the circulating levels in postmenopausal women of calcitonin, parathyroid hormone, the vitamin D metabolites 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D, and calcium and phosphate. The most striking finding was a sharp rise in the plasma levels of calcitonin. Estrogens are known to prevent postmenopausal bone loss but the mechanism of action remains obscure. We suggest that the beneficial effects of estrogens could be mediated, at least in part, through control of calcitonin secretion. Thus calcitonin may prove effective in the prevention of postmenopausal bone loss and its role in the treatment of established osteoporosis warrants further evaluation.

Physiology and Pathology of Bone Remodeling: Cellular Basis of Bone Structure in Health and in Osteoporosis

Physiology and Pathology of Bone Remodeling: Cellular Basis of Bone Structure in Health and in Osteoporosis