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Abstract: This narrative review analyzes the customization of menopause hormone therapy (MHT) for osteoporosis prevention and treatment in the context of the patients' age and menopausal age. In short, MHT is indicated in most women suffering from menopause before the age of 45 years except for breast cancer survivors. These women should be treated with MHT until the age of 50 years. For women who have entered menopause at around the age of 50 years, risks associated with MHT are low, and MHT is a safe option, provided there is an indication for it. We suggest that pursuing MHT entails different risks than initiating it, after the age of 60 years. In both cases, advantages and risks should be evaluated. We suggest using risk calculators to assess the magnitude of these risks and choosing regimens that entail the lowest breast and thrombosis risks., Competing Interests: Conflicts of Interest and Source of Funding: S.R. declares to have received funding from Abbott, Pfizer, Will, Gedeon Richter, MSD, Amgen, UCB Bayer, Mithra, Viatris for either research grants, speakers bureau, or advisory board participation. The other authors have no significant relationships with, or financial interest in, any commercial companies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Postmenopausal osteoporosis is a common condition and is associated with increased risk of fracture, including hip and vertebral fractures that in turn can have devastating consequences on morbidity and mortality. In this article, we review the pathogenesis and diagnostic approach to postmenopausal osteoporosis. We review available nonpharmacologic and pharmacologic therapies and we discuss their clinical efficacy and complications, with a detailed discussion of atypical femur fractures and osteonecrosis of the jaw.

Background: Cancer treatment-induced bone loss is an important long-term effect among breast cancer survivors. Little is known, however, about the pattern of bone loss and the factors associated with it., Objective: The aim of this study was to examine annual bone health changes and factors associated with bone loss for 3 years after diagnosis among women with breast cancer., Methods: Ninety-nine newly diagnosed women with breast cancer (mean age, 51.1 years) were enrolled in a prospective longitudinal study. Bone mineral density (BMD) was measured with dual-energy x-ray absorptiometry at baseline and yearly for 3 years., Results: During the 3-year follow-up, the proportion of women who had osteopenia or osteoporosis increased from 33.3% to 62.5%. The BMD of the participants significantly decreased 6.8% in the lumbar spine, 4.6% in the femur neck, and 3.5% in the total hip, with bone loss the greatest in the first year. In multiple linear regression analysis, chemotherapy was significantly associated with bone loss at all sites, and premenopausal status at diagnosis was significantly related to bone loss at the lumbar spine. We found no significant relationship between health behavior status and BMD change at any site., Conclusion: Women newly diagnosed with breast cancer can lose up to 6.8% of BMD during a 3-year follow-up. Chemotherapy and premenopausal status are important risk factors for bone loss., Implications for Practice: Identification of premenopausal women at diagnosis and monitoring BMD before and after chemotherapy are key for promoting bone health in women with breast cancer.

Because clinical trial data assessing more than 10 years of hormone therapy (HT) use are not available, providing guidance to menopausal women regarding duration of systemic HT is controversial. However, clinicians routinely encounter this issue in practice. Using available evidence and clinical experience, this chapter provides guidance for clinicians who care for patients who may be candidates for extended use of systemic HT.

Menopause occurring before the age of 40 harbors unique challenges as well as lifetime burden resulting from premature deprivation from ovarian hormones, primarily estrogen. Cessation of ovarian function before age 40 is considered premature (ovarian insufficiency), whereas if occurring before age 45, it is deemed "early." Early/premature menopause may be idiopathic, medically, or surgically induced. Regardless of the cause, for such women, menopausal hormone therapy is truly replacement and should continue until at least the average age of menopause. Hormone therapy offers the benefit of symptom control, and prevention of health consequences associated with premature loss of ovarian hormones.

Vasomotor symptoms are the most common manifestation of the menopause transition and postmenopausal phases of reproductive life. They interfere not only in quality of life, but also contribute to sleep and mood disturbances that potentially compromise home and work effectiveness. Treatment options include hormone therapy (HT), nonhormonal prescription drugs, mind body and behavior therapies, and over-the-counter preparations. Evidence confirms that HT is the most effective option. The initial reticence to prescribe HT immediately following publication of the Women's Health Initiative has been replaced by clear guidelines for confidently identifying women for whom this therapy will be safe.

Background: The aims of the present systematic review and meta-analysis were to evaluate published, randomized controlled trials that investigate the effects on whole-body vibration (WBV) training on total, femoral neck, and lumbar spine bone mineral density (BMD) in postmenopausal women, and identify the potential moderating factors explaining the adaptations to such training., Methods: From a search of electronic databases (PubMed, Web of Science, and Cochrane) up until September 2017, a total 10 studies with 14 WBV groups met the inclusion criteria. Three different authors tabulated, independently, the selected indices in identical predetermined forms. The methodological quality of all studies was evaluated according to the modified PEDro scale. For each trial, differences within arms were calculated as mean differences (MDs) and their 95% confidence intervals between pre- and postintervention values. The effects on bone mass between exercise and control groups were also expressed as MDs. Both analyses were performed in the total sample and in a specific class of postmenopausal women younger than 65 years of age (excluding older women)., Results: The BMD of 462 postmenopausal women who performed WBV or control protocol was evaluated. Significant pre-post improvements in BMD of the lumbar spine were identified following WBV protocols (P = .03). Significant differences in femoral neck BMD (P = .03) were also found between intervention and control groups when analyzing studies that included postmenopausal women younger than 65 years., Conclusions: WBV is an effective method to improve lumbar spine BMD in postmenopausal and older women and to enhance femoral neck BMD in postmenopausal women younger than 65 years.

Objective: To examine associations of several aspects of parity and history of lactation with incident hip fractures and clinical fractures and, in a subset of women, with bone mineral density., Methods: In this observational study, we analyzed data from 93,676 postmenopausal women participating in the Women's Health Initiative Observational Study and all bone density data from the subset of participants who underwent bone density testing at three clinical centers. At baseline, participants were aged 50-79 years. Using Cox proportional hazards regression analysis, we examined associations of fracture incidence and bone density with several aspects of parity (number of pregnancies, age at first pregnancy lasting 6 months or greater, and number of pregnancies lasting 6 months or greater) and breastfeeding (number of episodes of breastfeeding for at least 1 month, number of children breastfed, age when first breastfed, age when last breastfed, total number of months breastfed)., Results: The mean baseline age (standard deviation) of participants was 64 (±7.4) years (mean follow-up 7.9 years). During follow-up, the incident rate of hip fracture was 1.27%. Ten percent of participants were nulligravid. In fully adjusted models, number of pregnancies, parity, age at first birth, number of children breastfed, age at first breastfeeding, age at last breastfeeding, and total duration of breastfeeding were not statistically significantly associated with hip fracture incidence. There were no consistent associations of parity or lactation characteristics with overall clinical fracture risk or bone density. However, compared with never breastfeeding, a history of breastfeeding for at least 1 month was associated with a decreased risk of hip fracture (yes compared with no, hazard ratio 0.84, 95% confidence interval 0.73-0.98)., Conclusion: Patterns of parity and history of lactation were largely unrelated to fracture risk or bone density.

Prevention of osteoporosis should begin in childhood and continue throughout adulthood. Although genetic determinants of muscle and bone mass may offer other therapeutic options in the future, currently, counseling should primarily focus on lifestyle modification including healthy dietary practices and regular exercise. Vitamin supplementation, particularly vitamin D, should be considered to enhance diet based on patient's need. Attention to estrogen status is also important. In addition, patients should be counseled regularly about cigarette cessation and avoiding moderate alcohol intake.

This chapter provides a summary of the literature including results from large trials, meta-analyses, and recent major recommendations. Two well-accepted and recent recommendations include those from the Agency for Health Research and Quality on calcium and vitamin D supplementation and from the Institute of Medicine's dietary reference intakes for calcium and vitamin D. This review suggests that there is strong evidence for synergistic roles of calcium and vitamin D in maintaining bone health in postmenopausal women, but the correlation between vitamin D alone and bone health is overall inconclusive.

The purpose of this review is to evaluate current evidence regarding the use of dietary and exercise interventions to prevent fractures in postmenopausal women with osteoporosis. The key lifestyle modifications that can decrease risk of fracture in postmenopausal women include regular weight-bearing exercise and a balanced diet with adequate calcium and vitamin D intake. Other modifiable lifestyle factors critical to bone health and to decrease fracture risk include the avoidance of smoking, an excessively low body weight, excessive alcohol intake, and fall risks at home. Emerging modifiable factors may include B-vitamin, omega-3 fatty acid, soy isoflavone, and dehydroepiandrosterone supplementation.

Osteoporosis, a "silent disease," is often unrecognized until fracture. Lifestyle modification with nutritional counseling is recommended during menopausal transition. Bone density testing is recommended for women aged 65 years and older, younger postmenopausal women with risk factors, or to follow therapy. Bisphosphonates treat osteoporosis (prevent bone resorption). Raloxifene and hormone therapy prevent bone loss and fracture, with extraskeletal benefits. Denosumab treats osteoporosis, although bone effects reverse rapidly. Teriparatide (anabolic therapy) is considered for women at high risk of fracture. Bazedoxifene with conjugated estrogens, novel delivery of teriparatide, new parathyroid hormone proteins, anti-sclerostin antibodies, cathepsin K inhibitors, and stem cell therapies are in testing.

Introduction: Abundant animal and human evidence demonstrates that loading stimuli generate positive adaptive changes in bone, but effects of activity on bone mineral density (BMD) are often modest and frequently equivocal., Hypothesis: Physical activity effects on the femur would be better reflected in measurements of geometry than BMD., Study Design: Cross-sectional cohort study., Methods: We used data from 6032 women of mixed ethnicity aged 50-79 yr who had dual-energy x-ray absorptiometry (DXA) scans of the total body and hip from the Women's Health Initiative observational study. Subjects were distributed in three ways: self-report categories included 1) tertiles of MET and 2) reported minutes per week walking for exercise. A third, more objective, category was based on tertile of lean body mass fraction (LMF) from DXA scans. Femur outcomes included conventional femoral neck and total hip BMD, bone mineral content and region area, and geometry measurements using the Hip Structure Analysis software. Outcomes were compared between activity groups using models adjusted for common confounders., Results: Adjusted bone measurements showed similar activity effects with all three grouping variables, but these were greater and more significant when evaluated by LMF tertile. Women in the highest LMF tertile had the widest femurs. Differences in section modulus between highest and lowest tertile of LMF were 50%-80% greater than the association with bone mineral content and two to three times that on BMD., Conclusions: More active women in the Women's Health Initiative observational study had geometrically stronger femurs, although effects are underestimated, not apparent, or sometimes negative when using BMD as an outcome., Clinical Relevance: Exercise improves the strength of the femur largely by adding bone to the outer cortical surface; this improves resistance to bending, but because of the way DXA measurements are made, this may paradoxically reduce BMD.

There are many options available to address the quality of life and health concerns of menopausal women. The principal indication for hormone therapy (HT) is the treatment of vasomotor symptoms, and benefits generally outweigh risks for healthy women with bothersome symptoms who elect HT at the time of menopause. Although HT increases the risk of coronary heart disease, recent analyses confirm that this increased risk occurs principally in older women and those a number of years beyond menopause. These findings do not support a role for HT in the prevention of heart disease but provide reassurance regarding the safety of use for hot flushes and night sweats in otherwise healthy women at the menopausal transition. An increased risk of breast cancer with extended use is another reason short-term treatment is advised. Hormone therapy prevents and treats osteoporosis but is rarely used solely for this indication. If only vaginal symptoms are present, low-dose local estrogen therapy is preferred. Contraindications to HT use include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active liver disease. Alternatives to HT should be advised for women with or at increased risk for these disorders. The lowest effective estrogen dose should be provided for the shortest duration necessary because risks increase with increasing age, time since menopause, and duration of use. Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences.

Objective: To evaluate the efficacy of zoledronic acid in the prevention of bone loss in postmenopausal women with low bone mass., Methods: In this 2-year, randomized, multicenter, double-blind, placebo-controlled study, postmenopausal women with low bone mass were selected randomly to receive either zoledronic acid 5 mg intravenously at randomization and at month 12 (zoledronic acid 2 x 5 mg), zoledronic acid 5 mg intravenously only at randomization and placebo at month 12 (zoledronic acid 1 x 5 mg), or placebo at randomization and at month 12 (placebo). The primary efficacy endpoint was the percentage change in lumbar spine bone mineral density (BMD) (lumbar spine BMD) at month 24 relative to baseline., Results: Both zoledronic acid 2 x 5 mg and zoledronic acid 1 x 5 mg regimens significantly increased mean lumbar spine BMD compared with placebo at month 24 (5.18% and 4.42% compared with -1.32%, respectively, both P<.001). Similarly, significantly greater increases for both zoledronic acid regimens relative to placebo were observed for lumbar spine BMD at month 12 and for BMD at the proximal femur sites (total hip, femoral neck, trochanter) at month 12 and 24 (all P<.001). Both zoledronic acid regimens significantly reduced bone turnover markers over time relative to placebo (all P<.001), although changes with zoledronic acid 2 x 5 mg regimen were sustained greater during the second year relative to zoledronic acid 1 x 5 mg. The overall incidence of adverse events and serious adverse events were similar across all treatment groups., Conclusion: Both once-yearly dosing and a single dose of intravenous zoledronic acid 5 mg prevented bone loss for 2 years and were well-tolerated in postmenopausal women with low bone mass., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00132808., Level of Evidence: I.

An essential characteristic of advanced practice nurses is the use of theory in practice. Clinical nurse specialists apply theory in providing or directing patient care, in their work as consultants to staff nurses, and as leaders influencing and facilitating system change. Knowledge of technology and pharmacology has far outpaced knowledge of how to facilitate health behavior change, and new theories are needed to better understand how practitioners can facilitate health behavior change. In this article, the Integrated Theory of Health Behavior Change is described, and an example of its use as foundation to intervention development is presented. The Integrated Theory of Health Behavior Change suggests that health behavior change can be enhanced by fostering knowledge and beliefs, increasing self-regulation skills and abilities, and enhancing social facilitation. Engagement in self-management behaviors is seen as the proximal outcome influencing the long-term distal outcome of improved health status. Person-centered interventions are directed to increasing knowledge and beliefs, self-regulation skills and abilities, and social facilitation. Using a theoretical framework improves clinical nurse specialist practice by focusing assessments, directing the use of best-practice interventions, and improving patient outcomes. Using theory fosters improved communication with other disciplines and enhances the management of complex clinical conditions by providing holistic, comprehensive care.

Purpose of Review: Aromatase inhibitors improve survival in breast cancer patients but adversely affect bone health., Recent Findings: Hormone receptor positive breast cancer is increasingly targeted with chemotherapy, ovarian suppression and the use of aromatase inhibitors. Aromatase inhibitors block oestrogen production in peripheral tissues and the three third generation aromatase inhibitors (anastrozole, letrozole and exemestane) reduce circulating oestrogen levels, leading to accelerated bone loss and an increased risk of fracture.The majority of fractures occur in osteopaenic women prescribed aromatase inhibitors. Current guidelines advocate bone mineral density (BMD) measurement in all patients on aromatase inhibitors with selective use of antiresorptive therapy in osteoporotic (T-score > -2.5) women. Risk factors for premature bone loss and fracture include a low BMI, family history or personal history of fragility fracture after the age of 50, oral corticosteroid use more than 6 months and cigarette smoking. Emerging evidence supports concomitant use of bisphosphonates in all women on aromatase inhibitors to prevent fracture and breast cancer recurrence., Summary: The increasing use of aromatase inhibitors requires selection of patients for antiresorptive therapy and careful bone health management to reduce bone loss and prevent fragility fractures.

Evidence-based guidelines that have been prepared by many professional organizations aimed at assisting the clinician in the initial evaluation of postmenopausal women who should be considered for bone mineral density evaluation by dual-energy x-ray absorptiometry; history, physical examination, and laboratory testing in those women being considered for pharmacologic intervention; and monitoring and management of women for whom therapy is prescribed are discussed.

Objective: To determine if inequities in access to osteoporosis investigation [dual-energy x-ray absorptiometry (DXA) testing] and treatment (bisphosphonate, calcitonin, and/or raloxifene) exist among older women in a region with universal health care coverage., Methods: Community-dwelling women aged 65-89 years residing within 2 regions of Ontario, Canada were randomly sampled. Data were collected by standardized telephone interview. Potential correlates of DXA testing (verified by physician records), and current treatment were grouped by type as: "predisposing characteristics," "enabling resources," or "need factors" based on hypothesized relationships formulated before data collection. Variables associated with each outcome independent of "need factors" identified inequities in the system., Results: Of the 871 participants (72% response rate), 55% had been tested by DXA and 20% were receiving treatment. Using multiple variable logistic regression to adjust for need factors, significant inequities in access to DXA testing existed by age, health beliefs, education, income, use of preventive health services, region, and provider sex. DXA testing mediated access to treatment; 34% of those having had a DXA were treated compared with 2% of those who did not. Among women with osteoporosis, correctly reporting that their DXA test indicated osteoporosis and higher perceived benefits of taking pharmacological agents for osteoporosis were associated with treatment., Conclusions: Significant inequities in access to fracture prevention exist in a region with universal health care coverage. Improved access to DXA and better communication to patients of both their DXA results and the benefits of treatment has the potential to reduce the burden of osteoporosis.

No previous investigation has explored preventive behaviors among women with First-Degree Relatives (FDRs) diagnosed with osteoporosis, particularly Asian women. This study investigates osteoporosis knowledge, health beliefs and preventive behaviors of women with a family history of osteoporosis, and the different knowledge and health beliefs regarding preventive behaviors of women with such a history. Women were recruited at a large public health center in northern Taiwan. A questionnaire was administered to women with FDRs with osteoporosis with a focus on osteoporosis knowledge, health beliefs and preventive behaviors. Descriptive analysis was initially conducted. Correlation and differences between demographics, knowledge, health beliefs and preventive behaviors were rated for continuous variables, and the chi2 test was performed for categorical variables. A total of 251 who women satisfied the sampling criteria were invited to engage in the study. Two hundred and one women agreed to take part in the study, and the participation rate was around 80%. This work stresses the insufficiency of information on osteoporosis, constraining beliefs and ignorance of healthy preventive behaviors among women with FDRs with osteoporosis. Overall, the likelihood that women would take positive preventive behaviors is associated with their demographics and knowledge. The variables most strongly correlated with preventive behaviors for community-dwelling women are, in order, knowledge, number of children, educational level, knowledge of osteoporosis, experience of bone density examination, and whether or not women believed they had kyphosis. The results of this work can be applied to provide effective implementation guidelines for preventing osteoporosis, especially for women with a family history of the disease.

Recruitment of participants was a challenging issue for a statewide, 4-site, randomized, longitudinal trial for osteoporosis prevention. The accrual goal was 273 healthy breast cancer survivors. This federally funded study included a home-based followed by a fitness center-based 24-month intervention with follow-up at 36 months. In this report, recruitment planning, monitoring, and modifications are described, and the cost per enrolled participant is identified. Monthly monitoring of accrual numbers per recruitment strategy at each of 4 catchment areas allowed for early identification of necessary changes in recruitment strategies. Modifications were necessary when only 39% of the overall accrual goal had been attained at the 66% time point into the 18-month recruitment phase. Successful recruitment strategies were intensified, and new strategies were implemented, addressing motivators and deterrents for participation in clinical trials. Because approximately 81% of women were demonstrating bone loss via free dual energy x-ray absorptiometry screening, prevalence of the bone loss problem in survivors was incorporated into the recruitment information. Of 708 women screened via telephone and laboratory/dual energy x-ray absorptiometry testing, 249 were enrolled with 67% at 2 metropolitan sites and 33% at 2 rural sites. Recruitment media costs were approximately US$35 per enrolled participant. When combined with skeletal and laboratory screening, costs were approximately US$480 per enrolled participant. Tracking recruitment efforts in large clinical trials should be ongoing, site-specific, and cost-effective. Changes incorporated early in the recruitment phase addressed unique aspects of rural versus metropolitan areas and resulted in near achievement of accrual goals.

Purpose: To determine the impact of multipurpose exercise training on bone, body composition, blood lipids, physical fitness, and menopausal symptoms in early postmenopausal women with osteopenia., Methods: Forty-eight fully compliant (more than two sessions per week for 38 months) women (55.1 +/- 3.3 yr) without any medication or illness affecting bone metabolism took part in the exercise training (EG); 30 women (55.5 +/- 3.0 yr) served as the nontraining control group (CG). Both groups were individually supplemented with calcium and vitamin D. Bone mineral density (BMD) at various sites (lumbar spine, hip, forearm, calcaneus) was measured by dual x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). Maximal isometric and dynamic strength, maximal oxygen consumption (VO(2max)), CHD risk factors (blood lipids, body composition), and menopausal symptoms were determined., Results: After 38 months, significant differences between EG and CG were observed for the BMD at the lumbar spine (0.7% vs -3.0%) and the femoral neck (-0.7% vs -2.6%), body composition (waist circumference, waist-to-hip ratio), blood lipids (total cholesterol, triglycerides), and menopausal symptoms (insomnia, migraines, mood changes). Maximal isometric strength increased significantly by 10-36% in the EG, whereas, with one exception, changes in the CG were all negative. One-repetition maximum increased significantly at all sites measured (15-43%, P < 0.001). VO(2max) of the EG increased throughout the study with a significant 13.9 +/- 15.6% net increase after 3 yr. No significant changes after 3 yr could be observed in the CG., Conclusions: Our mixed high-intensity exercise program effectively compensates for most negative changes related to the menopausal transition.

Epidemiological studies that involve Asian women have revealed that their bone mineral density (BMD) is lower than that of European and American women. Few studies have simultaneously investigated the cognition, beliefs and behavior that affect BMD. The first aim of this study was to elucidate the relationships between demographics, knowledge of osteoporosis, health beliefs about osteoporosis, health-related behavior and BMD. The secondary goal was to explore the major predictive factors that affect the BMD of women in Community. This was an exploratory, community-based, cross-sectional study. Participants (N = 98) completed the osteoporosis related questionnaire and were invited to undergo BMD examinations using quantitative ultrasound (QUS). Overall, 73.4% of the participants had heard of the disease but the proportion of correct responses to the questions that tested knowledge of osteoporosis was only 44.0%. The investigation into osteoporosis-related beliefs revealed that women held quite accurate beliefs regarding the prevention of osteoporosis, but only 23.6% of them had undergone a BMD examination. An adjusted odds ratio indicated that if women had normal BMD then they were 1.57 times (95% CI: 1.08-2.29), 1.10 times (95% CI: 1.00-1.12) and 2.74 (95% CI: 1.09-6.86) times than their counterparts, respectively. The results revealed that women with normal BMD were more likely to have positively self-rated health, knowledge of osteoporosis and preventive behavior than their counterparts. The findings indicated that BMD was subjectively determined by a combination of cognitive and behavioral factors. Early detection was the key to preventing osteoporosis.

Menopausal women with epilepsy present several unique management challenges. They have an elevated risk for osteoporotic fracture because of the adverse effects of antiepileptic drugs (AEDs) on bone metabolism, combined with the chance of trauma during seizures and the subtle effects of AEDs on coordination that promote falling. A uniform effect of AEDs on vitamin D metabolism or bone turnover has not yet been revealed by clinical or basic studies, although the enzyme-inducing AEDs appear to decrease serum vitamin D levels. However, bone density is frequently decreased in patients with epilepsy. Clinicians must be familiar with the recommendations for calcium and vitamin D supplementation and recognize when to refer patients for bone density evaluations. Perimenopause is a transition during which women with epilepsy are at risk for increased seizure frequency, probably because of alterations in the estrogen:progesterone ratio over this period. Women with epilepsy who have had a catamenial seizure pattern during their reproductive years are at particular risk for an increase in seizure frequency during perimenopause but may experience a seizure reduction after becoming menopausal (cessation of menses for 1 year). These women appear to represent a subgroup of patients with epilepsy who have heightened sensitivity to endogenous reproductive hormone levels. The use of hormone replacement therapy may also increase seizure occurrence. Finally, the age at menopause may be reduced in women with poorly controlled seizures. This is probably related to an effect of seizures on hypothalamic function, although primary ovarian dysfunction may also be operative in this setting.

Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-MDP) in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free 99mTc-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTc-MDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the whole-skeleton plasma clearance of 99mTc-MDP (K(bone)). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-EDTA. The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663 (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological half-life of free 99mTc-MDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free 99mTc-MDP (K(total)=GFR+K(bone)), such that a larger value of K(total) was associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and K(bone). A strong inverse relationship was found between K(total) and the plasma concentration of free 99mTc-MDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow re-equilibration of bound MDP in the circulation. The results confirm that the fraction of free 99mTc-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K(bone) amongst other factors.

Objective: To evaluate the efficacy and safety of alendronate 35 mg once weekly compared with alendronate 5 mg daily in the prevention of osteoporosis., Methods: We compared the efficacy and safety of treatment with alendronate 35 mg once weekly (n = 362) and alendronate 5 mg daily (n = 361) in a 1-year, double-blind, multicenter study of postmenopausal women (6 months or greater), aged 40-70 years, with lumbar spine and femoral neck bone mineral density T-scores between -2.5 and 1. The primary efficacy end point was the comparability of lumbar spine bone mineral density increases, defined by strict prespecified criteria., Results: Mean increases in lumbar spine bone mineral density at 12 months were equivalent (difference between the alendronate 35-mg once-weekly group and the alendronate 5-mg daily group [90% confidence interval] at month 12 was -0.3% [-0.6, 0.1], well within the prespecified bounds of +/-1.0%). Bone mineral density increases at other skeletal sites and effects on bone turnover were also virtually identical for the two dosing regimens. Both treatment regimens were well tolerated, and the larger weekly unit dose was not associated with an increased frequency of upper gastrointestinal events., Conclusion: Alendronate 35 mg once weekly is therapeutically equivalent to alendronate 5 mg daily and provides patients with greater dosing convenience, in addition to the proven efficacy of alendronate and good tolerability.

Purpose: To determine the effect of an intense exercise training on physical fitness, coronary heart disease (CHD), bone mineral density (BMD), and parameters related to quality of life in early postmenopausal women with osteopenia., Methods: Fifty-nine fully compliant women (55.1 +/- 3.4 yr) without any medication or illness affecting bone metabolism took part in intensive exercise training (>2 sessions per week); 41 women served as nontraining control. Both groups received calcium and vitamin D (cholecalciferol) up to a maximum of 1500 mg x d(-1) calcium and 500 IU x d(-1) vitamin D. Bone density of the lumbar spine and hip (DXA Hologic QDR 4500), maximum isometric and dynamic strength (Schnell M3, Schnell-Trainer), VO2max (ZAN 600), and quality of life parameters including vasomotor symptoms related to menopause were measured at baseline and after 14 months., Results: After 14 months, there were significant differences between exercise and control groups concerning changes of bone density (LS exercise: +1.3%, P < 0.001 vs control: -1.2%, P < 0.001), maximum isometric strength (exercise: +11 to +32% (P < 0.001) vs control: -1.1 to +3.9%), VO2max (exercise: +11% (P < 0.001) vs control: -4% (P < 0.05)), and quality of life parameters (e.g., lower back pain). Dynamic strength (1RM tests) at four exercises, which was assessed in the exercise group only, increased significantly by 15-43% (all P < 0.001)., Conclusion: The intense exercise training program presented here was effective in improving strength, endurance, quality of life parameters, and even BMD in women in their critical early postmenopausal years.

The premature termination of one comparison in the Women's Health Initiative primary prevention trial due to stopping rules being reached necessitates a reconsideration of hormone replacement therapy (HRT). This part of the Women's Health Initiative trial, however, examined only one popular HRT regimen (conjugated equine estrogen [0.625 mg] and medroxyprogesterone acetate [2.5 mg] daily) in asymptomatic postmenopausal women. To help clinicians understand this large, complex trial, we describe several pervasive biases in earlier observational studies, review the principal findings of the trial, summarize recent systematic reviews, and offer clinical suggestions for HRT. Observational studies of HRT have found consistent, powerful protection against heart disease; this now appears due to consistent, powerful selection biases. These biases have the same net effect: Women using HRT in observational studies were healthier than those not using it. The Women's Health Initiative trial found that the overall risk-benefit ratio tipped against using HRT for prevention. Cardiovascular disease and breast cancer were increased among users, whereas colorectal cancer and osteoporotic fractures were reduced. Whether these findings relate to women with menopausal symptoms and to different HRT regimens is unknown. Hormone replacement therapy remains the best treatment for menopausal symptoms. Although estrogen has proven benefit for osteoporosis prevention, alternatives include raloxifene, alendronate, and risedronate. For women needing HRT, use of a low dose, with reassessments at least annually, appears prudent. Heart disease prevention strategies of proven value include exercise, weight control, blood pressure and lipid control, and avoidance of smoking. Hormone replacement therapy should not be used for this purpose.

Results of a recent meta-analysis of randomized trials suggest that, among postmenopausal women, the relative impact of hormone use in reducing the incidence of skeletal fracture declines with increasing age. We contend that: 1) the duration of the randomized trials in which older postmenopausal women were included was too short to adequately evaluate the impact of long-term hormone use on fracture risk; 2) randomized trials of hormone use in relation to a surrogate end point, bone mineral density, as well as nonrandomized studies of hormones and fracture risk, have documented a skeletal benefit associated with long-term hormone use among postmenopausal women irrespective of age; and 3) even if with increasing age there were a true decline in the relative benefit associated with the use of hormones, the size of the absolute reduction in fracture risk produced by hormone use among older postmenopausal women could be similar to or greater than that among younger postmenopausal women. For these reasons, we believe that when weighing the risks and benefits of the initiation or continuation of hormone therapy, a postmenopausal woman and her provider of health care need not consider her age when estimating the skeletal benefit such therapy can offer.

Postmenopausal survivors of breast cancer for whom hormone replacement therapy is contraindicated are at risk for development of osteoporosis. The primary purpose of this article is to describe, in a sample of 30 postmenopausal survivors of breast cancer, their calcium and vitamin D intake compared with recommended dietary guidelines for those nutrients for postmenopausal women not taking hormone replacement therapy and the body mass index of these women as nutritional status risk factors for development of osteoporosis. Bone health and presence of osteoporosis were determined by bone mineral density testing of the spine, hip, and forearm. To obtain calcium and vitamin D intake, including supplements, 3-day diet records were completed; height and weight measures were used to calculate body mass index. The sample participants ranged in age from 42 to 65 years; the majority (56%) had been menopausal or off hormone replacement therapy for 5 years or less, and 70% had completed breast cancer treatment for 5 years or less (except tamoxifen). The majority (63%) were of medium body frame size; 30% were of small frame size. The mean body mass index (27.3) and mean weight (160 lbs) indicate that these women, as a group, were over-weight. Although a large percent (63%) were taking calcium supplements, the mean daily intake (diet and supplements) of calcium (1,353 mg) and vitamin D (403 IU) was less than the recommended dietary guidelines for these nutrients in this population. At study entry, 80% of the women were osteopenic (60%) or osteoporotic (20%) and none was receiving treatment/prevention for osteoporosis; only 1 had a previous known osteoporosis diagnosis. This is a special group of women for whom screening and preventive strategies for osteoporosis are imperative.

Objectives: To study secondary osteoporosis postmenopause in women with hemiplegia and to show the therapeutic effects of etidronate and how osteoporotic conditions relate to the activities of daily living (ADL)., Design: Eighty-one postmenopausal women with hemiplegia were admitted within 6 mo of their first cerebrovascular accident. The bone mineral density (BMD) and biochemical markers of bone turnover were measured at the time of admission. Forty women (treatment group) received a 2-wk administration of etidronate. Forty-one women (control group) were not administered etidronate., Results: After completing a 3-mo rehabilitation program, BMD levels were remeasured. ADL was evaluated by FIM. The low ADL group had a larger decrease in BMD than the high ADL group. For the control group, the BMD rate of change on the paretic side of the femoral neck was -9.6%/3 mo for the low ADL group. BMD loss was reduced significantly by the administration of etidronate for the low ADL group., Conclusions: Results indicate that ADL corresponds to the progression of osteoporosis in postmenopausal women with hemiplegia and that increasing the level of ADL will reduce the progression of osteoporosis. Use of etidronate has also been proven to have a suppressive effect on the BMD decrease in women.

Osteoporosis is perhaps the widest-ranging social, physical, and economic impact of estrogen deficiency. Postmenopausal bone loss is the major determinant of osteoporosis. Osteoporotic risk can be determined by measuring bone mineral density using dual X-ray absorptiometry. The radiation free quantitative bone ultrasound is emerging in the assessment of bone structure giving reliable estimates of fracture risk. Diet and exercise are important in determining a woman's risks for osteoporosis. Hormone replacement therapy clearly decreases bone turnover and prevents postmenopausal bone loss and reduces fractures. Tibolone as well as raloxifene prevent bone loss and solid data demonstrate a reduction of vertebral fractures after raloxifene administration.

This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.

Objective: To determine the effects of four doses of a 7-day transdermal 17beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women., Methods: This was a multicenter, double-masked, randomized, placebo-controlled study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, proximal femur, and total hip measured with dual-energy x-ray absorptiometry. Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured., Results: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day resulted in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density of the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increases were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery system, effects of estrogen, and menopausal symptoms., Conclusion: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day effectively prevented bone loss in postmenopausal women.

Objective: To determine effectiveness of transdermal progesterone cream for controlling vasomotor symptoms and preventing postmenopausal bone loss., Methods: We randomly assigned 102 healthy women within 5 years of menopause to transdermal progesterone cream or placebo. Study subjects and investigators were masked until data analysis was completed. An initial evaluation included complete history, physical examination, bone mineral density determination, and serum studies (TSH, FSH, lipid profile, and chemistry profile). Subjects were instructed to apply a quarter teaspoon of cream (containing 20 mg progesterone or placebo) to the skin daily. Each woman received daily multivitamins and 1200 mg of calcium and were seen every 4 months for review of symptoms. Bone scans and serum chemistries were repeated after 1 year., Results: Thirty of the 43 (69%) in the treatment group and 26 of the 47 (55%) in the placebo group complained initially of vasomotor symptoms. Improvement or resolution of vasomotor symptoms, as determined by review of weekly symptom diaries, was noted in 25 of 30 (83%) treatment subjects and five of 26 (19%) placebo subjects (P < .001). However, the number of women who showed gain in bone mineral density exceeding 1.2% did not differ (alpha = .05, power of 80%)., Conclusion: Although we found no protective effect on bone density after 1 year, we did see a significant improvement in vasomotor symptoms in the treated group.

Objective: To define factors that identify patients at highest risk for osteoporosis who should be screened., Methods: We gave a questionnaire we developed for osteoporosis risk factors to 1346 menopausal women who were being screened by bone densitometry at the spine, hip, and femoral neck. Chi-square analysis using the one-tailed test was done on all categoric variables to determine differences or patterns in bone mineral density at specific sites. Multivariate logistic regression analysis was done on each of the three sites scanned to determine which combination of independent variables was a significant predictor of the presence or absence of osteoporosis., Results: Factors identified that were significant for the presence of osteoporosis were age 61 years or older, weight 165 pounds or less, or lack of any use of estrogen, either oral contraceptives or estrogen replacement therapy., Conclusion: We devised a simple system to identify which patients should be screened for osteoporosis.

Study Design: A 2-year randomized controlled trial., Objectives: To examine the possible preventive or aggravating effect of estrogen-progestin treatment on the back symptoms of slim premenopausal women with low lumbar spine bone mineral density., Summary of Background Data: The incidence of back pain, sciatica, or both starts to increase clearly among 45-54-year-old Finnish women., Methods: Forty-eight 39- to 49-year-old premenopausal women with a body mass index of 21 or less and a lumbar spine bone mineral density (L2-L4) of 1.1 +/- 1 g/cm3 or less compared with the normative population were recruited into the study. The women were assigned randomly to receive either estradiol-noretisteron acetate treatment or placebo. Back pain, symptoms, and disability were assessed with the Million and Oswestry questionnaires and pain drawings during the follow-up period at 0, 12, and 24 months. Inquiry also was made concerning previous back pain and sciatica history., Results: There was a statistically significant decrease in nighttime back pain (P < 0.001) and the total Oswestry disability scores (P < 0.004) in the hormone-treated group compared with the control group during the follow-up, but no statistically significant differences were found in daytime back pain. At baseline, the cumulative incidence in a history of pain radiating from the buttock to the foot in this osteopenic study group was 31/48, (64.5%; 95% CI 50.5-78.6), which is much more than the predicted 20/48, (42.4%; 95% CI 39.0-45.7) at this age according to a previous population study. The cumulative incidence of at least one back pain episode 44/48, (91.7%; 95% CI 83.6-99.8) was somewhat higher in these participants than was predicted for a comparative population of women this age, 38/48 (79.2%; 95% CI 70.2-87.3)., Conclusions: It seems that this regimen may have alleviating effects on nighttime back pain and functional back disability in slim osteopenic premenopausal women.

Osteoporosis is associated with fractures that result in morbidity and mortality and a large expenditure of health care resources. Given the large number of people at risk for the development of osteoporosis and the limited health care resources, it is imperative that clinically and economically favorable approaches to osteoporosis prevention and treatment be identified and implemented. The quantitative method of cost-effectiveness evaluation is one method of identifying favorable interventions. The importance of quality of life and the concept of quality-adjusted life years as an end point for assessing the effectiveness of interventions in osteoporosis is highlighted. The quality of life data critically needed to evaluate the impact of interventions in osteoporosis on quality-adjusted life years are discussed.

Osteoporosis is a bone disorder characterized by deficient bone mass and fragility fractures of the hip, wrist, and spine. The therapeutic strategies for treating osteoporosis are designed to maximize peak bone mass through proper nutrition, appropriate intake of calcium and vitamin D, maintenance of physiologic menstrual cycles, and a program of weight bearing and strengthening exercises. For the conditions of high bone turnover--osteoporosis in which osteoclastic resorption is increased--efficacious treatment options include hormone replacement therapy, calcitonin, and bisphosphonates. Osteoporosis with low bone turnover results from deficient osteoblastic bone formation and responds to the experimental drug programs of fluoride, parathyroid hormone, and parathyroid hormone related peptide analogues. Determination of bone density defines the patient's current condition, measurement of the level of N-telopeptides (collagen breakdown products) predicts the patient's future regarding osteoporotic fractures, and the presence of risk factors for hip fracture establish the therapeutic window for treatment.

The personal morbidity and economic burden associated with osteoporosis is substantial. Estrogen has been shown to have positive effects on the prevention and treatment of this disabling disease. Information is available with regard to when to initiate estrogen therapy, how long to maintain treatment, and how best to identify those women who will benefit most from its use.