The clinician's guide to prevention and treatment of osteoporosis.

Osteoporosis is the most common metabolic bone disease in the USA and the world. It is a subclinical condition until complicated by fracture(s). These fractures place an enormous medical and personal burden on individuals who suffer from them and take a significant economic toll. Any new fracture in an adult aged 50 years or older signifies imminent elevated risk for subsequent fractures, particularly in the year following the initial fracture. What a patient perceives as an unfortunate accident may be seen as a sentinel event indicative of bone fragility and increased future fracture risk even when the result of considerable trauma. Clinical or subclinical vertebral fractures, the most common type of osteoporotic fractures, are associated with a 5-fold increased risk for additional vertebral fractures and a 2- to 3-fold increased risk for fractures at other sites. Untreated osteoporosis can lead to a vicious cycle of recurrent fracture(s), often resulting in disability and premature death. In appropriate patients, treatment with effective antifracture medication prevents fractures and improves outcomes. Primary care providers and medical specialists are critical gatekeepers who can identify fractures and initiate proven osteoporosis interventions. Osteoporosis detection, diagnosis, and treatment should be routine practice in all adult healthcare settings. The Bone Health and Osteoporosis Foundation (BHOF) - formerly the National Osteoporosis Foundation - first published the Clinician's Guide in 1999 to provide accurate information on osteoporosis prevention and treatment. Since that time, significant improvements have been made in diagnostic technologies and treatments for osteoporosis. Despite these advances, a disturbing gap persists in patient care. At-risk patients are often not screened to establish fracture probability and not educated about fracture prevention. Most concerning, the majority of highest risk women and men who have a fracture(s) are not diagnosed and do not receive effective, FDA-approved therapies. Even those prescribed appropriate therapy are unlikely to take the medication as prescribed. The Clinician's Guide offers concise recommendations regarding prevention, risk assessment, diagnosis, and treatment of osteoporosis in postmenopausal women and men aged 50 years and older. It includes indications for bone densitometry as well as fracture risk thresholds for pharmacologic intervention. Current medications build bone and/or decrease bone breakdown and dramatically reduce incident fractures. All antifracture therapeutics treat but do not cure the disease. Skeletal deterioration resumes sooner or later when a medication is discontinued-sooner for nonbisphosphonates and later for bisphosphonates. Even if normal BMD is achieved, osteoporosis and elevated risk for fracture are still present. The diagnosis of osteoporosis persists even if subsequent DXA T-scores are above - 2.5. Ongoing monitoring and strategic interventions will be necessary if fractures are to be avoided. In addition to pharmacotherapy, adequate intake of calcium and vitamin D, avoidance of smoking and excessive alcohol intake, weight-bearing and resistance-training exercise, and fall prevention are included in the fracture prevention armamentarium. Where possible, recommendations in this guide are based on evidence from RCTs; however, relevant published data and guidance from expert clinical experience provides the basis for recommendations in those areas where RCT evidence is currently deficient or not applicable to the many osteoporosis patients not considered for RCT participation due to age and morbidity.

Forearm bone mineral density and fracture incidence in postmenopausal women with osteoporosis: results from the ACTIVExtend phase 3 trial.

Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. INTRODUCTION: Abaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend. METHODS: Ultradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method. RESULTS: At cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs - 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant). CONCLUSION: Ultradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01657162 submitted July 31, 2012.

VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation.

UNLABELLED: The aim was to meta-analyze randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention. Meta-analysis showed a significant 15 % reduced risk of total fractures (summary relative risk estimate [SRRE], 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). INTRODUCTION: Calcium plus vitamin D supplementation has been widely recommended to prevent osteoporosis and subsequent fractures; however, considerable controversy exists regarding the association of such supplementation and fracture risk. The aim was to conduct a meta-analysis of randomized controlled trials [RCTs] of calcium plus vitamin D supplementation and fracture prevention in adults. METHODS: A PubMed literature search was conducted for the period from July 1, 2011 through July 31, 2015. RCTs reporting the effect of calcium plus vitamin D supplementation on fracture incidence were selected from English-language studies. Qualitative and quantitative information was extracted; random-effects meta-analyses were conducted to generate summary relative risk estimates (SRREs) for total and hip fractures. Statistical heterogeneity was assessed using Cochran's Q test and the I (2) statistic, and potential for publication bias was assessed. RESULTS: Of the citations retrieved, eight studies including 30,970 participants met criteria for inclusion in the primary analysis, reporting 195 hip fractures and 2231 total fractures. Meta-analysis of all studies showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures (SRRE, 0.85; 95 % confidence interval [CI], 0.73-0.98) and a 30 % reduced risk of hip fractures (SRRE, 0.70; 95 % CI, 0.56-0.87). Numerous sensitivity and subgroup analyses produced similar summary associations. A limitation is that this study utilized data from subgroup analysis of the Women's Health Initiative. CONCLUSIONS: This meta-analysis of RCTs supports the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.

Longitudinal association of measures of adiposity with serum antioxidant concentrations in postmenopausal women.

BACKGROUND/OBJECTIVES: The relationship between obesity and circulating levels of antioxidants is poorly understood. Most studies that have examined the association of adiposity with blood or tissue concentrations of antioxidant micronutrients have been cross-sectional, and few have compared the associations for indices of overall obesity and central obesity. Our aim was to prospectively examine the longitudinal association of body mass index (BMI), waist circumference (WC), waist circumference-height ratio (WCHtR) and waist-hip ratio (WHR) with major serum antioxidants in a population of postmenopausal women. SUBJECTS/METHODS: We used a subsample of participants in the Women's Health Initiative aged 50-79 years at entry with available fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up (N=2672). Blood samples were used to measure α-carotene, ß-carotene, ß-cryptoxanthin, lutein+zeaxanthin, α-tocopherol, γ-tocopherol and retinol at baseline, and at years 1, 3 and 6. We used mixed-effects linear regression analyses to examine associations between anthropometric measures and serum antioxidants at baseline and over time, controlling for covariates. RESULTS: In longitudinal analyses, carotenoids, and particularly ß-carotene, were strongly and inversely associated with BMI, WC and WCHtR and less so with WHR. α-Tocopherol showed a strong positive association with WHR but not with other anthropometric measures, whereas γ-tocopherol was positively and strongly associated with BMI, WC, WCHtR and less so with WHR. Retinol was positively associated with WHR. The inverse association of several carotenoids with anthropometric measures was stronger in never and former smokers compared with current smokers and in women without the metabolic syndrome. The inverse association of carotenoids with obesity measures may reflect reduced micronutrient concentrations owing to inflammation associated with obesity. CONCLUSIONS: In the present study, the strongest observed associations between anthropometric variables and micronutrients were an inverse association of WC with serum ß-carotene and a positive association of WC with γ-tocopherol.

Clinician's Guide to Prevention and Treatment of Osteoporosis.

The Clinician's Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.

Celiac disease is not increased in women with hip fractures and low vitamin D levels.

OBJECTIVE: Celiac disease is associated with decreased bone density; however, the risk of fractures in celiac disease patients is unclear. We compared the prevalence of celiac disease between a group of women with hip fractures and a group of women undergoing elective joint replacement surgery and the association between celiac disease and vitamin D levels. METHODS: Two hundred eight community dwelling and postmenopausal women were recruited from Boston, MA (n=81) and Baltimore, MD (n=127). We measured tissue transglutaminase IgA by ELISA to diagnose celiac disease and 25-hydroxyvitamin D (25(OH)D) levels by radioimmunoassay in both women with hip fractures (n=157) and a control group (n=51) of total hip replacement subjects from Boston. Subjects were excluded if they took any medications or had medical conditions that might affect bone. RESULTS: Median serum 25(OH)D levels were significantly lower (p< 0.0001) in the hip fracture cohorts compared to the elective joint replacement cohort (14.1 ng/ml vs. 21.3 ng/ml, respectively). There were no differences in the percentage of subjects with a positive tissue transglutaminase in the women with hip fractures versus the control group (1.91% vs. 1.96%, respectively). CONCLUSION: Vitamin D levels are markedly reduced in women with hip fractures, however hip fracture patients did not show a higher percentage of positive tissue transglutaminase levels compared with controls. These data suggest that routine testing for celiac disease among hip fracture patients may not be necessary in the absence of clinical signs and symptoms, although data from larger studies among hip fracture subjects are needed.

Systems-based approaches to osteoporosis and fracture care: policy and research recommendations from the workgroups.

Participants in the conference selected to attend two different working group sessions. The working groups discussed different perspectives of system-based approaches to osteoporosis and fracture care. The group on postfracture case management recommended that nurse case managers be used to improve communication among patients, orthopaedic surgeons, and those providing ongoing clinical care. The hospital working group discussed the impact of and barriers to improved postfracture management in the hospital setting. The health systems group emphasized the difference between a closed system in which long-term benefits of interventions were more likely to be appreciated than in fee for service systems. The health information technology group discussed the advantages and challenges of electronic health records. The working group on consumer and provider education discussed interventions for both primary and secondary prevention of fractures. Recommendations were produced by most groups for improving postfracture care.

Ethnic differences in femur geometry in the women's health initiative observational study.

SUMMARY: Participants in the observational study of the Women's Health Initiative (WHI) were studied to determine if ethnic differences in femur geometry can help to explain differences in hip fracture rates. Structural differences in femurs of African and Mexican-American women appear to be consistent with lower rates of hip fractures vs. whites. INTRODUCTION: Ethnic origin has a major influence on hip fractures, but the underlying etiology is unknown. We evaluated ethnic differences in hip fracture rates among 159,579 postmenopausal participants in the WHI then compared femur bone mineral density (BMD) and geometry among a subset with dual X-ray absorptiometry (DXA) scans of the hip and total body. METHODS: The subset included 8,206 non-Hispanic whites, 1,476 African-American (AA), 704 Mexican-American (MA), and 130 Native Americans (NA). Femur geometry derived from hip DXA using hip-structure analysis (HSA) in whites was compared to minority groups after adjustment for age, height, weight, percent lean mass, neck-shaft angle and neck length, hormone use, chronic disease (e.g., diabetes, rheumatoid arthritis, cancer), bone active medications (e.g., corticosteroids, osteoporosis therapies), and clinical center. RESULTS: Both AA and MA women suffered hip fractures at half the rate of whites while NA appeared to be similar to whites. The structural advantage among AA appears to be due to a slightly narrower femur that requires more bone tissue to achieve similar or lower section moduli (SM) vs. whites. This also underlies their higher BMD (reduces region area) and lower buckling ratios (buckling susceptibility). Both MA and NA women had similar advantages vs. whites at the intertrochanter region where cross-sectional area and SM were higher but with no differences at the neck. NA and MA had smaller bending moments vs. whites acting in a fall on the hip (not significant in small NA sample). Buckling ratios of MA did not differ from whites at any region although NA had 4% lower values at the IT region. CONCLUSION: Differences in the geometry at the proximal femur are consistent with the lower hip fracture rates among AA and MA women compared to whites.

Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.

Vitamin D-deficiency and post-fracture changes in lower extremity function and falls in women with hip fractures.

UNLABELLED: We determined the prevalence of vitamin D deficiency and lower extremity function in women with hip fractures. Women with extremely low vitamin D levels had reduced lower extremity muscle function and increased falls 1 year later. Ensuring vitamin D sufficiency after a hip fracture may improve function and reduce falls. INTRODUCTION: Hip fractures are the most devastating of fractures, commonly leading to loss of independent ambulation and living. In this retrospective analysis we determined the prevalence of vitamin D deficiency in women with hip fractures and the association between 25-hydroxyvitamin D [25(OH)D] levels and functional impairment one year later. METHODS: One hundred ten community-dwelling women with hip fractures were recruited from Boston, MA (n = 30) and Baltimore, MD (n = 80) before 1998 and 25(OH)D levels were measured by radioimmunoassay. In a subset of women from Baltimore, a performance measure of the lower extremities using the lower extremity gain scale (LEGS) was measured at 2, 6, and 12 months. Falls, grip strength, chair rise time, walking speed, and balance were also determined. RESULTS: Vitamin D insufficiency defined as a 25(OH)D 9 ng/mL, those with 25(OH)D

Importance of vitamin D in hospital-based fracture care pathways.

OBJECTIVES: This project was developed to identify ways to support hospital-based improvements for the identification and management of osteoporosis following treatment of a fragility fracture. DESIGN: This is a retrospective review of medical records of sets of consecutive patients who were admitted for surgical treatment of fragility fracture following introduction of several versions of admission and discharge care pathways. Effectiveness of the admission pathway was defined as % subjects with measurement of serum 25- hydroxyvitamin D (25(OH)D) during hospitalization; effectiveness of the discharge pathway was defined as % subjects with documentation of instructions for calcium and/or vitamin D supplementation. SETTING: This study reviewed medical records of patients admitted to hospital for surgical treatment of a fragility fracture. PARTICIPANTS: Medical records were evaluated for 98 patients older than 50-years who were admitted with a fragility fracture of the hip or femur. MEASUREMENTS: Medical records were reviewed for the % subjects with documentation of an in-hospital order for serum 25(OH)D and with documentation of instructions to patients upon discharge concerning calcium and vitamin D intake. Median value of serum 25(OH)D was calculated. RESULTS: In accordance with the admission pathway, serum 25(OH)D was measured in 37% (36/98). The median 25(OH)D level was 19.5 ng/mL; 78% were vitamin D insufficient [serum 25(OH)D < or = 32 ng/mL] and 58% were vitamin D deficient [serum 25(OH)D < or = 20 ng/mL]. In accordance with the discharge pathway, 74% (71/96) were discharged on calcium and/or vitamin D. CONCLUSION: The high prevalence of vitamin D insufficiency (78%) observed in this study affirms the importance of incorporating vitamin D supplementation in hospital-based fracture care pathways. The discharge pathway was more effective than the newer admission pathway, a finding attributable to effects of familiarity, retraining, and introduction of computer-prompts. These evolving pathways represent a much-needed paradigm shift in the care of fragility fracture patients.

Correlation of plain radiographic indices of the hip with quantitative bone mineral density.

UNLABELLED: Radiographic parameters of the hip can be useful as an indication of bone mineral density at the femoral neck. Measurements available from routine hip radiographs were correlated with DXA values. Although radiographs are not a test for osteoporosis, measurements of cortical thickness provide information useful for referral for osteoporosis assessment. INTRODUCTION: Plain hip radiographs are widely used for evaluation of hip pathology in osteoarthritis. A purpose of this study was to determine whether there are relationships between radiographic parameters of bone structure and bone mineral density T-scores, as assessed by dual energy x-ray absorptiometry (DXA). METHODS: Pre-operative radiographs of 32 postmenopausal, osteoarthritic women undergoing hip arthroplasty were evaluated. Radiographic parameters including the Singh index, Dorr classification, canal-to-calcar ratio, and cortical thickness indices (CTI) were measured and compared with T-score, serum 25 hydroxyvitamin D levels, body mass index (BMI), and body weight. RESULTS: The T-score at the femoral neck for type C bone was significantly lower than that of type A (p = 0.041). The CTIs were correlated positively with T-scores for anteroposterior radiographs (r = 0.5814, p = 0.0005), and for lateral radiographs (r = 0.571, p = 0.0006). A threshold for lateral CTI set at a value of < or =0.40 results in sensitivity of 0.85 and specificity of 0.79 to segregate the osteoporotic and non-osteoporotic patients. CONCLUSION: Femurs with small radiographic cortical thickness indices had lower T-scores. Finding a radiographic hip cortical thickness index (LAT) with a value of < or =0.40 should be an alert for referral for osteoporosis evaluation and bone mineral density testing.

Bone cross-sectional geometry in adolescents and young women with anorexia nervosa: a hip structural analysis study.

INTRODUCTION: Better characterization of bone geometry in adolescents with anorexia nervosa (AN) may improve understanding of skeletal deficits in this population. Our objective was to determine whether hip cross-sectional geometry and bone strength were altered in adolescents with AN. METHODS: Measurements of the left total proximal femur and body composition were obtained in 85 adolescents with AN and 61 healthy controls by dual X-ray absorptiometry. The Hip Structural Analysis (HSA) program was used to determine aBMD, cross-sectional area (CSA), and section modulus (Z) at the femoral neck and shaft. Strength indices were calculated and corrected for lean mass. RESULTS: Femoral neck and shaft aBMD were lower in AN patients than healthy controls (-36% and -29%, p < 0.001). In both regions, bone CSA and Z were lower in AN sufferers (-11 to -35%, p < 0.001). While lean body mass correlated with HSA variables (r = 0.48 to 0.58, p < 0.001), body fat did not. AN sufferers had lower indices of both whole bone strength (-40%, p < 0.001) and relative bone strength (-36%, p < 0.001) than controls. CONCLUSIONS: Anorexia nervosa sufferers had decreased resistance to axial (CSA) and bending loads (Z) compared with healthy controls. Differences in strength properties were significant even when adjusted for lean mass, suggesting that not only decreased mechanical loading, but also known metabolic differences are likely responsible for deficits in bone strength in these patients.

Relationship between insulin-like growth factor I, dehydroepiandrosterone sulfate and proresorptive cytokines and bone density in cystic fibrosis.

INTRODUCTION: Patients with cystic fibrosis (CF) are known to be at risk for early osteoporosis, and the mechanisms that mediate bone loss are still being delineated. The aim of the present investigation was to investigate if a correlation exists in these patients between skeletal measurements by dual-energy x-ray absorptiometry (DXA) and two anabolic factors, dehydroepiandrosterone (DHEA) and insulin-like growth factor I (IGF-I), and proresorptive factors such as the cytokines interleukin-1beta, tumor necrosis factor alpha, and interleukin-6. METHODS: We studied 32 outpatients (18 females; mean age: 26.2+/-7.9 years) at a tertiary care medical center. The subjects had venous samples obtained, underwent anthropometric and bone mineral density (BMD) measurements, and completed a health survey. Serum IGF-I concentrations were below the age-adjusted mean in 78% of the participants, and DHEA sulfate (DHEAS) concentrations were low in 72%. Serum concentrations of all cytokines were on the low side of normal; nonetheless, there was a modest inverse correlation between IL-1beta and BMD at all sites. RESULTS: In univariate analyses, IGF-I and DHEAS were significant correlates of BMD or bone mineral content. In final multivariate models controlling for anthropometric and other variables of relevance to bone density, only IGF-I was identified as a significant independent skeletal predictor. While alterations in DHEAS, IGF-I, and specific cytokines may contribute to skeletal deficits in patients with CF, of these factors a low IGF-I concentration appears to be most strongly correlated with BMD. CONCLUSIONS: These findings may have therapeutic implications for enhancing bone density in these patients.

Fractures in the elderly and vitamin D.

Aging is associated with increased fracture risk. Among the many contributing factors, reduced bone mineral density is highly correlated with this risk. Nutritional factors, i.e. protein, calcium, and vitamin D intake, are essential for maintenance of the skeleton throughout the lifespan and are often compromised in the elderly. Vitamin D is also derived from conversion of precursors in the skin that is stimulated by sunlight. Decreased mobility and avoidance of the sun contribute to vitamin D deficiency in the elderly. The skeletal effects of vitamin D are two-fold: it ensures mineralization of the organic matrix of bone and it mediates mobilization of stored calcium and phosphate from bone to blood to achieve mineral homeostasis. Inadequate levels of vitamin D produce a secondary increase in release of parathyroid hormone that stimulates bone resorption and can result in osteoporosis. If coupled with insufficient intake of calcium, vitamin D deficiency results in osteomalacia. With aging, there is reduced absorption of the vitamin from the diet, reduced conversion to its active metabolites, and resistance to its action in the intestine and in bone. Correction of vitamin D deficiency is an inexpensive task and may require education of clinicians as well as the public. In sum, vitamin D deficiency is prevalent in the elderly and, to correct the adverse skeletal effects, it should be diagnosed, treated, and prevented.

Effects of inhaled glucocorticoids on bone density in premenopausal women.

BACKGROUND: Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma. METHODS: We studied 109 premenopausal women, 18 to 45 years of age, who had asthma and no known conditions that cause bone loss and who were treated with inhaled triamcinolone acetonide (100 microg per puff). We measured bone density by dual-photon absorptiometry at base line, at six months, and at one, two, and three years. Serum osteocalcin and parathyroid hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured serially. We measured inhaled glucocorticoid use by means of monthly diaries, supported by the use of an automated actuator-monitoring device. RESULTS: Inhaled glucocorticoid therapy was associated with a dose-related decline in bone density at both the total hip and the trochanter of 0.00044 g per square centimeter per puff per year of treatment (P= 0.01 and P=0.005, respectively). No dose-related effect was noted at the femoral neck or the spine. Even after the exclusion of all women who received oral or parenteral glucocorticoids at any time during the study, there was still an association between the decline in bone density and the number of puffs per year of use. Serum and urinary markers of bone turnover or adrenal function did not predict the degree of bone loss. CONCLUSIONS: Inhaled glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal women.

Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer.

PURPOSE: We sought to evaluate the effects of chemotherapy-induced ovarian failure on bone loss and markers of skeletal turnover in a prospective longitudinal study of young women with breast cancer receiving adjuvant chemotherapy. PATIENTS AND METHODS: Forty-nine premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated within 4 weeks of starting chemotherapy (baseline), and 6 and 12 months after starting chemotherapy with dual-energy absorptiometry and markers of skeletal turnover osteocalcin and bone-specific alkaline phosphatase. Chemotherapy-induced ovarian failure was defined as a negative pregnancy test, greater than 3 months of amenorrhea, and a follicle-stimulating hormone > or = 30 MIU/mL at the 12-month evaluation. RESULTS: Among the 35 women who were defined as having ovarian failure, highly significant bone loss was observed in the lumbar spine by 6 months and increased further at 12 months. The median percentage decrease of bone mineral density in the spine from 0 to 6 months and 6 to 12 months was -4.0 (range, -10.4 to +1.0; P =.0001) and -3.7 (range, -10.1 to 9.2; P =.0001), respectively. In contrast, there were no significant decreases in bone mineral density in the 14 patients who retained ovarian function. Serum osteocalcin and bone specific alkaline phosphatase, markers of skeletal turnover, increased significantly in the women who developed ovarian failure. CONCLUSION: Chemotherapy-induced ovarian failure causes rapid and highly significant bone loss in the spine. This may have implications for long-term breast cancer survivors who may be at higher risk for osteopenia, and subsequently osteoporosis. Women with breast cancer who develop chemotherapy-induced ovarian failure should have their bone density monitored and treatments to attenuate bone loss should be evaluated.