Management Of Postmenopausal Osteoporosis Research Articles

Management of Postmenopausal Osteoporosis for Primary Care

Management of Postmenopausal Osteoporosis for Primary Care

Potential Therapeutic Use of Cytokines in Gynaecology and Obstetrics

Therapeutic manipulation of cytokines may be accomplished by inhibition of a particular cytokine using an antagonist or by administering the cytokine itself. Cytokines appear to have a number of physiological roles, and consequently therapeutic implications, in obstetrics and gynaecology. In the central nervous system, interleukin-1 (IL-1) decreases gonadotropin releasing hormone and luteinising hormone levels and increases prolactin levels. Interferon-alpha and -gamma and tumour necrosis factor-alpha have negative effects on sperm motility and penetration rates. Seminal IL-6 and IL-8 levels correlate negatively with fertility. IL-8 seems to be involved in periovulatory events by attracting and activating neutrophils that play a role in timely follicular rupture. Leukaemia inhibitory factor has been shown to be essential for blastocyst implantation. Interleukin-1 may be one of the signals for the onset of human parturition, and may also play a role in the initiation of preterm labour associated with intra-amniotic infection. In a mouse model, pretreatment with subcutaneous IL-1 receptor antagonist (IL-1ra) prevented IL-1-induced preterm parturition, suggesting a role for the use of anticytokine agents in the treatment of infection-associated preterm labour. IL-8 induces cervical ripening when applied locally to the cervix in rabbits, which indicates its pivotal role in cervical maturation. The evaluation of cytokine levels, especially IL-1, may be used as a diagnostic tool to monitor osteoporosis, and drugs such as IL-1ra that interfere with cytokine action could provide new therapies for the effective management of postmenopausal osteoporosis. In spite of all these possibilities, current cytokine-based therapies are still experimental, and numerous problems need to be resolved before they are used in routine clinical applications.

Effects of prolonged bisphosphonate therapy and its discontinuation on bone mineral density in post-menopausal osteoporosis

OBJECTIVE The bisphosphonates have proven efficacy in the management of post-menopausal osteoporosis. However, the benefits of prolonged (> 2 years) administration and the effects of discontinuation of bisphosphonate treatment are not clear. DESIGN We have previously reported a 2-year, randomized, double-blind, placebo-controlled trial of pamidronate therapy (150 mg/day) in women with established post-menopausal osteoporosis. We now report the bone mineral density (BMD) changes in those women who continued for a third year of active treatment and were then observed off therapy for a further 12 months. PATIENTS Twenty-two women (mean age 66 years) continued on pamidronate in year 3, and in 16 of these the effects of subsequent discontinuation of therapy for 12 months were studied. MEASUREMENTS BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer. RESULTS The third year of therapy with pamidronate was associated with a significant further gain in BMD only at the lumbar spine (2.1 +/- 0.6%, P = 0.003), resulting in a total gain of 9.5 +/- 1.0% at that site over 3 years of treatment. In the total body, BMD tended to decline (-0.6 +/- 0.3%) in year 3. One year after discontinuation of pamidronate, there were significant losses of BMD in the total body (-1.9 +/- 0.3%, P < 0.0001) and femoral trochanter (-2.7 +/- 0.9%, P = 0.01), and non-significant changes at the lumbar spine (-0.9 +/- 0.8%), femoral neck (-0.5 +/- 1.6%), and Ward's triangle (-2.9 +/- 3.7%). By the end of one year off therapy, BMD was greater than baseline only in the lumbar spine (7.1 +/- 1.1%, P < 0.0001) and femoral trochanter (4.5 +/- 1.88%, P < 0.03). In the total body, BMD was 0.3 +/- 0.7% below the values at the trial's inception (P = 0.7). CONCLUSIONS These data demonstrate that the rate of bone gain associated with bisphosphonate use slows over time, and that significant bone loss follows withdrawal of these agents. These findings have important implications for the duration of use of these novel drugs in the therapy of osteoporosis and suggest a need for close observation following their discontinuation.

Effects of Prolonged Bisphosphonate Therapy and Its Discontinuation on Bone Mineral Density in Post-Menopausal Osteoporosis

Orr-Walker, Brandon; Wattie, Diana J.; Evans, Margaret C.; Reid, Ian R. Author Information

Effects of prolonged bisphosphonate therapy and its discontinuation on bone mineral density in post-menopausal osteoporosis.

The bisphosphonates have proven efficacy in the management of post-menopausal osteoporosis. However, the benefits of prolonged (> 2 years) administration and the effects of discontinuation of bisphosphonate treatment are not clear. We have previously reported a 2-year, randomized, double-blind, placebo-controlled trial of pamidronate therapy (150 mg/day) in women with established post-menopausal osteoporosis. We now report the bone mineral density (BMD) changes in those women who continued for a third year of active treatment and were then observed off therapy for a further 12 months. Twenty-two women (mean age 66 years) continued on pamidronate in year 3, and in 16 of these the effects of subsequent discontinuation of therapy for 12 months were studied. BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer. The third year of therapy with pamidronate was associated with a significant further gain in BMD only at the lumbar spine (2.1 +/- 0.6%, P = 0.003), resulting in a total gain of 9.5 +/- 1.0% at that site over 3 years of treatment. In the total body, BMD tended to decline (-0.6 +/- 0.3%) in year 3. One year after discontinuation of pamidronate, there were significant losses of BMD in the total body (-1.9 +/- 0.3%, P < 0.0001) and femoral trochanter (-2.7 +/- 0.9%, P = 0.01), and non-significant changes at the lumbar spine (-0.9 +/- 0.8%), femoral neck (-0.5 +/- 1.6%), and Ward's triangle (-2.9 +/- 3.7%). By the end of one year off therapy, BMD was greater than baseline only in the lumbar spine (7.1 +/- 1.1%, P < 0.0001) and femoral trochanter (4.5 +/- 1.88%, P < 0.03). In the total body, BMD was 0.3 +/- 0.7% below the values at the trial's inception (P = 0.7). These data demonstrate that the rate of bone gain associated with bisphosphonate use slows over time, and that significant bone loss follows withdrawal of these agents. These findings have important implications for the duration of use of these novel drugs in the therapy of osteoporosis and suggest a need for close observation following their discontinuation.

Therapy of Osteoporosis: Calcium, Vitamin D, and Exercise

<h2>ABSTRACT:</h2> Calcium supplementation has long been regarded as a fundamental part of the prevention and treatment of postmenopausal osteoporosis, but it is only in recent years that clear evidence has emerged demonstrating its impact on bone mass. Calcium supplementation does not completely arrest postmenopausal bone loss but slows the rate of decline by 30 to 50%. The effect of calcium supplementation on fracture incidence in post-menopausal women has not been established. Vitamin D deficiency is common in the frail elderly, particularly in countries where fortification or food with this vitamin is not practiced. Treatment of vitamin D deficiency has been associated with significant reductions in the number of hip fractures. The role of the potent vitamin D metabolites, calcitriol and alphacalcidol, in the management of postmenopausal osteoporosis is not clear. Although some studies show substantial benefits in bone density or fracture rate from the use of these compounds, the published data are inconsistent. In general, hormone replacement therapy and the potent bisphosphonates produce greater effects on bone density and there is a greater consistency among the results of the published studies of these other interventions. Controlled trials of exercise interventions in postmenopausal women show that exercise can positively influence bone density by a few percent. Exercise interventions in the elderly have been reported to decrease fall frequency by 10%. This latter effect may have a greater impact on fracture frequency than the modest benefits of exercise on bone density.

Therapy of osteoporosis: calcium, vitamin D, and exercise.

Calcium supplementation has long been regarded as a fundamental part of the prevention and treatment of postmenopausal osteoporosis, but it is only in recent years that clear evidence has emerged demonstrating its impact on bone mass. Calcium supplementation does not completely arrest postmenopausal bone loss but slows the rate of decline by 30 to 50%. The effect of calcium supplementation on fracture incidence in postmenopausal women has not been established. Vitamin D deficiency is common in the frail elderly, particularly in countries where fortification or food with this vitamin is not practiced. Treatment of vitamin D deficiency has been associated with significant reductions in the number of hip fractures. The role of the potent vitamin D metabolites, calcitriol and alphacalcidol, in the management of postmenopausal osteoporosis is not clear. Although some studies show substantial benefits in bone density or fracture rate from the use of these compounds, the published data are inconsistent. In general, hormone replacement therapy and the potent bisphosphonates produce greater effects on bone density and there is a greater consistency among the results of the published studies of these other interventions. Controlled trials of exercise interventions in postmenopausal women show that exercise can positively influence bone density by a few percent. Exercise interventions in the elderly have been reported to decrease fall frequency by 10%. This latter effect may have a greater impact on fracture frequency than the modest benefits of exercise on bone-density.

P015 Integrated management of postmenopausal osteoporosis in a regional centre in hungary

P015 Integrated management of postmenopausal osteoporosis in a regional centre in hungary

Management of postmenopausal osteoporosis

Postmenopausal osteoporosis is associated with significant morbidity, mortality, reduction in quality of life, and increasing health care costs. It is estimated that 1.5 million women in the United States have one or more osteoporosis-related fractures annually. Fractures may occur at any site, but vertebral fractures are the most common. Longitudinal studies have demonstrated a decreased life expectancy associated with both vertebral and nonvertebral fractures. Once an initial fracture occurs, there is a fivefold increased risk of a second fracture within 1 year. The management of osteoporosis today incorporates multiple modalities of therapy. In addition to early detection, patient education, exercise, and nutritional supplementation, multiple therapeutic agents should be implemented early in an attempt to prevent initial and subsequent fractures. This article reviews currently approved modalities of therapy for the prevention and treatment of postmenopausal osteoporosis.

The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women

To assess the effect of the antiestrogenic agent tamoxifen on bone mineral density in normal late postmenopausal women. A randomized, double-blind, placebo-controlled trial was performed with 57 healthy, late postmenopausal women (mean 11 +/- 7 years since menopause). Subjects were assigned to take either tamoxifen 20 mg/d or placebo for 2 years. Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, trochanter) bone mineral densities were measured every 6 months using dual-energy x-ray absorptiometry. Serum and urine indices of bone turnover were measured at baseline, 6 months, and 2 years. In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 1.4%, while that in the women given placebo declined by 0.7% (P < 0.01 for difference between groups). Total body bone mineral density declined in both groups, but less so in the tamoxifen-treated women (P < 0.05). At both sites, the effect of tamoxifen was maximal after 1 year, with no further separation of the groups thereafter. There was no significant effect of tamoxifen on bone mineral density in the proximal femur. Tamoxifen produced significant falls in serum alkaline phosphatase (P < 0.0001), ionized calcium (P < 0.0001), and phosphate (P < 0.01), and in urinary excretion of hydroxyproline, n-telopeptides, and calcium (P < 0.05 for each). In normal late postmenopausal women, tamoxifen at a dose of 20 mg/d exerts a small protective effect on bone mineral density, comparable in magnitude to that of calcium supplementation and less than that of either estrogen or the bisphosphonates. Tamoxifen is unlikely to supersede any of these therapies in the management of postmenopausal osteoporosis.

Management of postmenopausal osteoporosis

More than 25% of postmenopausal women are at risk of osteoporosis. In order to avoid its consequences, it is necessary to find an appropriate prevention and/or treatment. We studied: (1) 15 postmenopausal women treated with percutaneous estradiol (50 μg/24 h) plus MPA (10 mg/10 days/month); (2) 15 postmenopausal women treated with synthetic calcitonin nasal spray at the daily dose of 100 IU; (3) 10 postmenopausal women treated with nandrolone decanoate (50 mg every 3 weeks); (4) 10 postmenopausal women treated with ipriflavone (600 mg/day); and (5) 10 postmenopausal women treated with sodium fluoride (20 mg) plus calcium (600 mg). Clinical examination, bone mass measurement (total BMD), hematochemical and urinary parameters of bone metabolism (calcium, urinary hydroxyproline, PTH) and growth factors (as IGF-I and TNF-β) were evaluated. After 6 months of therapy, a complete prevention of bone resorption was achieved. In agreement with current literature, we observed that the various therapeutic approaches have all some positive effect on BMD, with different results on pain, blood biochemical parameters and growth factors' concentrations.

Slow-Release Sodium Fluoride in the Management of Postmenopausal Osteoporosis

To test whether intermittent treatment with slow-release sodium fluoride and continuous calcium citrate supplementation inhibits vertebral fractures without causing fluoride complications. A placebo-controlled, randomized trial. Outpatient setting of specialty clinics in Dallas and Temple, Texas. Slow-release sodium fluoride (25 mg twice daily) in repeated 14-month cycles (12 months on treatment followed by 2 months off treatment) compared with placebo. Both groups took calcium citrate (400 mg calcium twice daily) continuously. 110 patients with postmenopausal osteoporosis were randomly assigned to two groups. In the slow-release sodium fluoride group, 48 of 54 patients completed more than 1 cycle of treatment (mean, 2.44 cycles/patient), whereas 51 of 56 patients in the placebo group completed at least 1 cycle (mean, 2.14 cycles/patient) in this interim analysis. Vertebral fracture rate and lumbar bone mineral content. Vertebral fractures were quantified from yearly radiographs. Bone mass was determined annually by densitometry. In the sodium fluoride group, the mean L2 to L4 bone mineral content increased by 4% to 6% in each cycle and the mean femoral neck bone density increased by 4.1% and 2.1% during the first two cycles, but the radial bone density did not change. The placebo group showed no statistical change in bone mass at any site. Compared with the placebo group, the sodium fluoride group had a lower individual new vertebral fracture rate (0.057/patient cycle compared with 0.204/patient cycle, P = 0.017), a higher fracture-free rate (83.3% compared with 64.7%, P = 0.042), and a lower group fracture rate (0.085/patient cycle compared with 0.239/patient cycle, P = 0.006). The side-effect profile was similar for the two groups; no patient developed microfractures, hip fractures, or blood loss anemia. Intermittent slow-release sodium fluoride plus continuous calcium citrate, administered for about 2.5 years, inhibits new vertebral fractures, increases the mean spinal bone mass without decreasing the radial shaft bone density, and is safe to use.

Effects of progesterone on postovariectomy bone loss in aged rats

The effects of progesterone on oophorectomy-induced bone loss in aged rats were evaluated. Female rats aged 12 months were divided into three groups: (1) sham-operated controls (SHAM); (2) oophorectomized (OVX); (3) OVX rats treated with progesterone (OVX + PROG). After 20 weeks the dry weight, bone ash, and calcium content of femur, tibia, and fourth lumbar vertebra were significantly lower in OVX than in sham rats. These reductions did not occur in OVX rats treated with PROG. There was no difference in the bone composition between the control and progesterone-treated rats. Vertebral bone histomorphometry showed increased bone resorption as well as increased bone formation parameters in OVX rats. Progesterone treatment inhibited the increased resorption indices, but the bone formation remained elevated. The results indicate that progesterone therapy prevents the postovariectomy bone loss in aged rats. The protective effect of progesterone is mediated by inhibition of bone resorption while maintaining the increased bone formation. These findings suggest that progesterone alone may be a valuable agent for management of postmenopausal osteoporosis.