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Obesity is a risk factor for chronic diseases and moderate weight loss is generally recommended. Energy restriction results in the loss of hip bone mineral density (BMD) in older adults, but there is no consistent decline at the lumbar spine (LS), possibly due to vertebral abnormalities although this may also be dependent on the amount of weight loss. In this secondary analysis of weight loss trials investigating BMD and trabecular bone score (TBS) changes over 12-18 months, 92 postmenopausal women (60.8 ± 5.8 years; body mass index 32.7 ± 4.4 kg/m

Objective Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. In May 2018, denosumab was approved for the treatment of GIOP in men and women at high risk of fracture. We undertook a systematic review and meta-analysis to summarize the efficacy and safety of denosumab in the prevention and treatment of GIOP. Methods We searched PubMed, CINAHL, American College of Rheumatology and American Society for Bone and Mineral Research meeting abstracts for relevant studies. We included studies in which subjects were taking systemic glucocorticoid therapy and were assigned to take denosumab or control therapy, and assessed the effect of treatment on areal bone mineral density (BMD), fractures and/or safety. Results Three eligible studies were included in the primary meta-analysis. Denosumab significantly increased lumbar spine BMD (2.32%, 95% CI 1.73%, 2.91%, P

Context We previously found that variation in a quantitative trait locus, including the gene-encoding endothelin-converting enzyme 1 (Ece1), accounted for 40% of the variance in bone biomechanics and bone mineral density (BMD) in an intercross of recombinant congenic mouse strains. Objective We hypothesized that single nucleotide polymorphisms (SNPs) within the human ECE1 isoform b promoters, at ECE1 b −338(G/T) and ECE1 b −839(A/C), would associate with osteoporosis in postmenopausal women. Design We genotyped DNA for the ECE1 −338(G/T) and −839(A/C) SNPs. Setting A community medical center. Participants Postmenopausal women (3564) with ≥1 dual-energy X-ray absorptiometry scan ≥60 years of age. Main Outcome Measures BMD, osteoporosis, and clinical fractures. Results In multivariate models controlling for age, weight, healthcare duration, and tobacco, the CC genotype reduced the odds of lifetime fracture (OR 0.33, 95% CI 0.12, 0.87) and fracture ≥50 years of age (OR 0.31, 95% CI 0.11, 0.87), whereas the AC genotype increased odds of osteoporosis (OR 1.34, 95% CI 1.02 1.78) relative to the AA genotype. However, when controlling the false-discovery rate, findings were no longer significant. We found no consistent relationship between the ECE1 b −338(G/T) and study outcomes. Conclusions The CC genotype was associated with fewer fractures, whereas the AC genotype was associated with osteoporosis. Our small sample size and few minorities are study limitations. Findings should be tested in another cohort to confirm a link between the ECE1 −839(A/C) SNPs and osteoporosis.

Doctors do not know whether treatment of high parathyroid hormone levels is linked to better outcomes in their patients with kidney disease. In this study, lower parathyroid hormone levels at baseline were linked to lower risk of fracture, vascular events, and death in people with kidney disease. Chronic kidney disease (CKD) affects ~ 20% of older adults, and secondary hyperparathyroidism (HPT) is a common condition in these patients. To what degree HPT predicts fractures, vascular events, and mortality in pre-dialysis CKD patients is debated. In stage 3 and 4 CKD patients, we assessed relationships between baseline serum PTH levels and subsequent 10-year probabilities of clinical fractures, vascular events, and death. We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients receiving care between 1985 and 2013, and whose PTH was measured using a second-generation assay. Covariates included PTH, age, gender, tobacco use, vascular disease, diabetes, hypertension, hyperlipidemia, obesity, GFR, and use of osteoporosis medications. Five thousand one hundred eight subjects had a mean age of 68 ± 17 years, 48% were men, and mean follow-up was 23 ± 10 years. Fractures, vascular events, and death occurred in 18%, 71%, and 56% of the cohort, respectively. In univariate and multivariate models, PTH was an independent predictor of fracture, vascular events, and death. The hazards of fracture, vascular events and death were minimized at a baseline PTH of 0, 69, and 58 pg/mL, respectively. We found that among individuals with stage 3 and 4 CKD, PTH was an independent predictor of fractures, vascular events, and death. Additional epidemiologic studies are needed to confirm these findings. If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating HPT reduces the risk of fracture, vascular events, and death.

Objective Cardiovascular disease (CVD) is accelerated in patients with systemic lupus erythematosus and lupus nephritis (LN). Despite the literature suggesting that renal arteriosclerosis predicts CVD in other glomerulonephritis diseases, arteriosclerosis grading and reporting might be particularly overlooked in LN biopsies. Our objective was to examine the burden of renal arteriosclerosis in LN and to assess whether arteriosclerosis is underreported in LN biopsies. Methods We identified all patients with LN undergoing kidney biopsy between 1994 and 2017 at an academic center. We interpreted LN biopsy reports to classify the Banff categories of absent, mild, moderate, or severe renal arteriosclerosis. The prevalence of renal arteriosclerosis was compared with the prevalence published for age-matched healthy peers, and predictors of arteriosclerosis were examined. We overread biopsies for Banff renal arteriosclerosis grading and compared to pathology reports. Results Among 189 incident patients with LN, renal arteriosclerosis prevalence was 2 decades earlier compared to their healthy peers, affecting 40% of patients ages 31-39 years with LN compared to 44% of healthy peers ages 50-59 years. A multivariable analysis showed a 3-fold higher odds of renal arteriosclerosis in patients ages ≥30 years with LN. LN chronicity on biopsy results predicted a 4-fold higher odds of renal arteriosclerosis. The overreads determined that 50% of standard LN biopsy reports missed reporting the presence or absence of renal arteriosclerosis. Conclusion Renal arteriosclerosis is accelerated by 2 decades in patients with LN compared to their healthy peers and is overlooked by pathologists in half of the routine biopsy reports. We propose incorporating Banff renal arteriosclerosis grading in all LN biopsy reports.

In the field of human nutrition, randomized controlled trials (RCTs) are considered the gold standard for establishing causal relations between exposure to nutrients, foods, or dietary patterns and prespecified outcome measures, such as body composition, biomarkers, or event rates. Evidence-based dietary guidance is frequently derived from systematic reviews and meta-analyses of these RCTs. Each decision made during the design and conduct of human nutrition RCTs will affect the utility and generalizability of the study results. Within the context of limited resources, the goal is to maximize the generalizability of the findings while producing the highest quality data and maintaining the highest levels of ethics and scientific integrity. The aim of this document is to discuss critical aspects of conducting human nutrition RCTs, including considerations for study design (parallel, crossover, factorial, cluster), institutional ethics approval (institutional review boards), recruitment and screening, intervention implementation, adherence and retention assessment, and statistical analyses considerations. Additional topics include distinguishing between efficacy and effectiveness, defining the research question(s), monitoring biomarker and outcome measures, and collecting and archiving data. Addressed are specific aspects of planning and conducting human nutrition RCTs, including types of interventions, inclusion/exclusion criteria, participant burden, randomization and blinding, trial initiation and monitoring, and the analysis plan.

We proposed the term "dysmobility syndrome" (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The Osteoporotic Fractures in Men (MrOS) study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of the Fracture Risk Assessment Tool (FRAX). Men met DS criteria at baseline if they had three or more of the following: appendicular lean mass/height2 30%, spine or hip T-score ≤ -2.5, grip strength

The American College of Physicians (ACP) recently updated their clinical practice guidelines for the treatment of low bone density and osteoporosis. These guidelines, aimed at generalists, importantly emphasize the critical nature of osteoporosis and provide a basic framework to guide its management. We support the ACP's effort to improve awareness and treatment of osteoporosis. However, we would like to address some important limitations encompassed by the six ACP recommendations that are particularly relevant to specialists, such as rheumatologists. This article is protected by copyright. All rights reserved.

Impaired intestinal calcium absorption contributes to osteoporosis, but its measurement is limited to research settings. We hypothesized that 24-hour urine calcium (24HUC) values could diagnose low fractional calcium absorption (FCA). We performed a post hoc analysis of clinical trial data to determine whether 24HUC predicted low FCA compared with the gold standard dual calcium isotope method. Two hundred thirty postmenopausal women

Purpose of review The clinical benefits of vitamin D therapy have received substantial attention over the past decade. Recently, several trials looked to clarify the optimal vitamin D dose or serum level needed to promote human health. The purpose of this review is to highlight selected studies published since January 2015. Recent findings Several recent trials challenge whether serum vitamin D levels at least 30 ng/ml promote human health. In postmenopausal women with 25-hydroxyvitamin D [25(OH)D] levels 21 ± 3 ng/ml, high-dose vitamin D for 1 year increased calcium absorption by 1%, without changes in bone mineral density, physical function, or falls when compared with low-dose vitamin D and placebo. High-dose vitamin D increased risk of falling in 200 adults 78 ± 5 years old with baseline 25(OH)D levels of ∼19 ± 9 ng/ml. High-dose vitamin D in adults increased the number and duration of upper respiratory tract infections compared with placebo. Asthma patients achieving 25(OH)D levels more than 30 ng/ml during a trial experienced more respiratory infections than those not achieving such levels. Summary Recent studies are congruent with the Institute of Medicine's conclusion that humans are vitamin D replete when their serum 25(OH)D levels are at least 20 ng/ml. Higher levels seem to promote falls and respiratory infections.

Hypercalcemia most often results from primary hyperparathyroidism and malignancy. Adynamic bone disease (ABD) is a form of renal osteodystrophy characterized by reduced bone turnover, which can limit the ability of bone to release or store calcium, potentially leading to low, normal, or high serum calcium levels. We describe a 51‐year‐old dialysis‐dependent female with hypercalcemia after parathyroidectomy. A demeclocycline‐labeled bone biopsy confirmed adynamic bone disease. Teriparatide, a recombinant form of parathyroid hormone (PTH) used to treat postmenopausal osteoporosis, was prescribed for 12 months and normalized serum calcium levels. Although previous case reports and series have described favorable changes in spine bone mineral density when teriparatide was prescribed for ABD, ours is the first documented case in which teriparatide resolved hypercalcemia due to ABD. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Background Despite the pivotal role hydroxychloroquine (HCQ) plays in treating SLE, less than 50% of patients take HCQ as prescribed. Non-adherence versus lack of effect to HCQ are difficult to distinguish, underscoring the importance of measuring HCQ blood levels to assess adherence. Despite this, information and consensus on the clinical impact of incorporating routine testing of HCQ blood levels is lacking. Therefore, we systematically reviewed publications examining the correlation between 1) HCQ levels and adherence, and 2) HCQ levels and SLEDAI scores, in SLE patients. We hypothesized that low HCQ levels would correlate with non-adherence and higher SLEDAI scores. Methods A comprehensive search was performed using MeSH heading and keywords in Medline, Embase, CINHL and Web of Science databases. We selected observational and interventional studies that measured HCQ levels and assessed adherence and/or SLEDAI scores in adults with SLE. Newcastle Ottawa Scale and Cochrane Collaboration Risk Assessment tools were used to rate the quality of observational and intervention studies, respectively. We used Forest plots to compare pooled estimates (95% CI) of correlations between HCQ levels and patient or physician reported nonadherence and SLEDAI scores. Heterogeneity was assessed using I2. Results From 306 manually reviewed studies, four studies analyzing correlation between HCQ levels and adherence, and five studies examining the correlation between SLEDAI and HCQ blood levels, met inclusion criteria. The odds of nonadherence measured by physician or reported by the patient was 3 times higher in patients with below threshold HCQ levels, compared to those with higher HCQ levels (OR 2.95, 95% CI 1.63, 5.35, p Conclusions We found good correlation between HCQ levels and non-adherence. Low HCQ levels showed higher mean SLEDAI scores but due to the limited number of studies and heterogeneity we did not find significant correlation. Findings support the clinical utility of measuring HCQ levels in SLE patients. Future larger studies should investigate standards for HCQ level interpretation and target levels needed to minimize SLEDAI scores. Funding Source(s): n/a

Although systemic lupus erythematosus (SLE) most commonly occurs in reproductive-age women, some are diagnosed after the age of 50. Recognizing that greater than one-third of SLE criteria are cutaneous, we undertook a systematic review and meta-analysis to evaluate differences in cutaneous manifestations in early- and late-onset SLE patients.We searched the literature using PubMed, CINAHL, Web of Science, and Cochrane Library. We excluded studies that did not include ACR SLE classification criteria, early-onset controls, that defined late-onset SLE as50 years of age, or were not written in English. Two authors rated study quality using the Newcastle Ottawa Quality Scale. We used Forest plots to compare odds ratios (95% CI) of cutaneous manifestations by age. Study heterogeneity was assessed using I(2).Overall, 35 studies, representing 11,189 early-onset and 1727 late-onset patients with SLE, met eligibility criteria. The female:male ratio was lower in the late-onset group (5:1 versus 8:1). Most cutaneous manifestations were less prevalent in the late-onset group. In particular, malar rash [OR = 0.43 (0.35, 0.52)], photosensitivity [OR = 0.72 (0.59, 0.88)], and livedo reticularis [OR = 0.33 (0.17, 0.64)] were less common in late-onset patients. In contrast, sicca symptoms were more common [OR = 2.45 (1.91, 3.14)]. The mean Newcastle Ottawa Quality Scale score was 6.3 ± 0.5 (scale: 0-9) with high inter-rater reliability for the score (0.96).Overall, cutaneous manifestations are less common in late-onset SLE patients, except sicca symptoms. Future studies should investigate etiologies for this phenomenon including roles of immune senescence, environment, gender, and immunogenetics.

Objective Despite increased cardiovascular disease (CVD) risk, rheumatoid arthritis (RA) patients often lack CVD preventive care. We examined CVD preventive care processes from RA patient and provider perspectives to develop a process map for identifying targets for future interventions to improve CVD preventive care. Methods Thirty-one participants (15 patients, 7 rheumatologists, and 9 primary care physicians [PCPs]) participated in interviews that were coded using NVivo software and analyzed using grounded theory techniques. Results Patients and providers reported that receipt of preventive care depends upon identifying and acting on risk factors, although most noted that both processes rarely occurred. Engagement in these processes was influenced by various provider-, system-, visit-, and patient-related conditions, such as patient activation or patients’ knowledge about their risk. While nearly half of patients and PCPs were unaware of RA-CVD risk, all rheumatologists were aware of risk. Rheumatologists reported not systematically identifying risk factors, or, if identified, they described communicating about CVD risk factors via clinic notes to PCPs instead of acting directly due to perceived role boundaries. PCPs suggested that scheduling PCP visits could improve CVD risk management, and all participants viewed comanagement positively. Conclusion Findings from this study illustrate important gaps and opportunities to support identifying and acting on CVD risk factors in RA patients from the provider, system, visit, and patient levels. Future work should investigate professional role support through improved guidelines, patient activation, and system-based RA-CVD preventive care strategies.

Minimal treatment options exist for idiopathic muscle cramps.We evaluated whether correction of vitamin D insufficiency relieved muscle cramps in postmenopausal women.We conducted a post hoc analysis of a randomized, double-blind, placebo-controlled trial at a single academic medical center in the Midwest to evaluate the benefits of treating vitamin D insufficiency. Two hundred thirty postmenopausal women participated. Eligible women were ≤75 years old, 5 years past menopause or oophorectomy, or ≥60 years if they had previously undergone hysterectomy without oophorectomy. Women had vitamin D insufficiency at baseline (25-hydroxyvitamin D 14-27 ng/mL). We excluded subjects with a glomerular filtration rate45 mL/minute.Participants completed food diaries, laboratory studies, and functional tests including the Timed Up and Go test, Physical Activity Scale for the Elderly, Health Assessment Questionnaire (a measure of disability), and pain scores. Subjects recorded muscle cramp frequency and severity using a standardized form at 6 visits over 1 year.During the trial, over half of participants (n=121, 53%) reported muscle cramps. Despite unequivocal vitamin D repletion, vitamin D had no effect on muscle cramps. Pain levels, disability, and dietary potassium predicted presence of cramps. Serum albumin and physical activity were inversely associated with, and disability was positively associated with, severity of muscle cramps.Further studies are needed to evaluate the link between pain, disability, dietary potassium intake, and muscle cramps.

Background Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). Objective To determine if there are differences in BMD and body composition between male and female participants with PKU. Methods From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15–50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16–35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1–3 weeks each. Results Male participants had significantly lower mean total body BMD Z-scores (means ± SE, males = − 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1–4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above − 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = − 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. Conclusions Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258., Highlights • Males with PKU showed lower total body BMD and tended to excrete more calcium in urine compared to females with PKU. • Males with PKU had low-normal lean body mass and females with PKU had greater fat mass than males. • Our data suggest that males with PKU may be at greater risk for osteoporosis than females with PKU.

We proposed the term “dysmobility syndrome” (DS) to identify individuals with impaired musculoskeletal health, a risk factor for falls and fractures. Whether DS is associated with increased risk of incident fracture is unknown. The “Osteoporotic Fractures in Men” study enrolled 5994 men ages ≥65 years, between March 2000 and April 2002. We used baseline data to determine whether DS increased fracture risk, independent of FRAX. Men met DS criteria at baseline if they had ≥3 of the following: appendicular lean mass/height(2) 30%, spine or hip T-score ≤−2.5, grip strength

Publisher's version (útgefin grein), Background: Although osteoporosis is an easily diagnosed and treatable condition, many individuals remain untreated. Clinical decision support systems might increase appropriate treatment of osteoporosis. We designed the Osteoporosis Advisor (OPAD), a computerized tool to support physicians managing osteoporosis at the point-of-care. The present study compares the treatment recommendations provided by OPAD, an expert physician and the National Osteoporosis Guideline Group (NOGG). Methods: We performed a retrospective analysis of 259 patients attending the outpatient osteoporosis clinic at the University Hospital in Iceland. We entered each patient's data into the OPAD and recorded the OPAD diagnostic comments, 10-year risk of major osteoporotic fracture and treatment options. We compared OPAD recommendations to those given by the osteoporosis specialist, and to those of the NOGG. Results: Risk estimates made by OPAD were highly correlated with those from FRAX (r = 0.99, 95% CI 0.99, 1.00 without femoral neck BMD; r = 0.98, 95% CI, 0.97, 0.99 with femoral neck BMD. Reassurance was recommended by the expert, NOGG and the OPAD in 68, 63 and 52% of cases, respectively. Likewise, intervention was recommended by the expert, NOGG, and the OPAD in 32, 37 and 48% of cases, respectively. The OPAD demonstrated moderate agreement with the physician (kappa 0.51, 95% CI 0.41, 0.61) and even higher agreement with NOGG (kappa 0.69, 95% CI 0.60, 0.77). Conclusion: Primary care physicians can use the OPAD to assess and treat patients' skeletal health. Recommendations given by OPAD are consistent with expert opinion and existing guidelines., This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

© 2017, American College of Rheumatology Objective: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP). Methods: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence. We used a group consensus process to determine the final recommendations and grade their strength. The guideline addresses initial assessment and reassessment in patients beginning or continuing long-term (≥3 months) glucocorticoid (GC) treatment, as well as the relative benefits and harms of lifestyle modification and of calcium, vitamin D, bisphosphonate, raloxifene, teriparatide, and denosumab treatment in the general adult population receiving long-term GC treatment, as well as in special populations of long-term GC users. Results: Because of limited evidence regarding the benefits and harms of interventions in GC users, most recommendations in this guideline are conditional (uncertain balance between benefits and harms). Recommendations include treating only with calcium and vitamin D in adults at low fracture risk, treating with calcium and vitamin D plus an additional osteoporosis medication (oral bisphosphonate preferred) in adults at moderate-to-high fracture risk, continuing calcium plus vitamin D but switching from an oral bisphosphonate to another antifracture medication in adults in whom oral bisphosphonate treatment is not appropriate, and continuing oral bisphosphonate treatment or switching to another antifracture medication in adults who complete a planned oral bisphosphonate regimen but continue to receive GC treatment. Recommendations for special populations, including children, people with organ transplants, women of childbearing potential, and people receiving very high-dose GC treatment, are also made. Conclusion: This guideline provides direction for clinicians and patients making treatment decisions. Clinicians and patients should use a shared decision-making process that accounts for patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Background Worldwide, an osteoporosis (OP) care gap exists for individuals with a fragility fracture (FF). Published data shows that US veterans are no exception. To address the OP care gap, fracture liaison services (FLS) are being implemented with the goal to prevent additional FF. Objectives Here we report the patient outcomes after initiating a FLS at a US Veterans Affairs (VA) hospital. Methods We identified veterans with a pelvic, hip and/or femur shaft fracture by querying a central database. Veterans with traumatic fractures, active OP medication, recent dual-energy X-ray absorptiometry (DXA) and/or hospice status were excluded. The remaining veterans were contacted via letter and the responsible primary health care team was sent a template letter with OP management recommendations via the electronic medical record. Recommendations included DXA, laboratory evaluation, and pharmacologic and non-pharmacologic interventions. In most cases, trained clinical pharmacists serving as FLS coordinators performed all tasks with an expert physician available for questions. Presented data are based on a review 4 months after recommendations were sent. Results The initial query revealed 149 veterans with pelvic, femoral, and/or hip fractures without a recent DXA and/or active OP therapy. Of those, 32 (31 males, 1 female) patients suffered a FF and were included in the FLS intervention. Our review showed that 59% of these had a DXA scan, 35% had their calcium/vitamin D intake reviewed, and 40% had started OP therapy or were referred to an OP specialist. When the primary care team9s clinical pharmacist instead of the primary care provider implemented the FLS recommendations (10/32), 100% of the recommendations were addressed. Furthermore, 70% of patients had a bisphosphonate ordered, whereas it was 9% when no pharmacist was involved (p=0.0004). Conclusions Our study suggests that a pharmacist-led FLS improves post-FF care in US veterans. We found a high percentage of OP care goals met when patients interacted with clinical pharmacists. This observation might be due to the fact that most pharmacists had dedicated training in OP management and their interaction with the patient focused on their FF. In summary, our data suggests that clinical pharmacists trained in OP management can very effectively implement a FLS intervention. Disclosure of Interest None declared

Background Osteoporosis, obesity and sarcopenia are risk factors for fractures and their combination has a negative effect on musculoskeletal health (MSKH). We proposed a score-based approach to define this combination as “dysmobility syndrome (DS)”. DS increases mortality in the NHANES cohort but no data exist on fracture risk. The most widely used fracture risk calculator, the WHO FRAX® tool, does not include several measures of MSKH such as physical function, muscle mass or falls. In this analysis of the Osteoporotic Fractures in Men (MrOS) cohort, we examine whether individuals with impaired MSKH/DS have a higher incidence of fragility fractures and whether this composite score confers additional risk for fracture, beyond risk estimates provided by FRAX®. Objectives In this analysis of the Osteoporotic Fractures in Men (MrOS) cohort, we examine whether individuals with impaired MSKH/DS have a higher incidence of fragility fractures and whether this composite score confers additional risk for fracture, beyond risk estimates provided by FRAX®. Methods The MrOS cohort was utilized in this study. The score-based approach to define DS includes six factors with one point assigned to each: appendicular lean mass/height2 30%, T-score ≤-2.5, grip strength Results 5827 men ages 74±6 years with a mean BMI of 27.4±3.8 kg/m2 had complete data necessary for this analysis. 391 males (6.7%) met criteria for DS. 571 (10%) experienced a MOF including 245 (4%) hip fractures. DS increased the hazards of major osteoporotic (HR 3.31, 95% CI, 2.58, 4.23) and hip (HR 3.48, 95% CI 2.41, 5.03) fractures. In adjusted models, DS and elevated FRAX® risk each increased the hazards of major osteoporotic and hip fracture. Interaction models showed no significant interaction between the presence of DS and FRAX® score for major osteoporotic (p=0.184) or hip (p=0.177) fractures. Conclusions DS was associated with increased MOF fracture incidence even after adjusting for quartiles of FRAX® risk in this cohort of older men. Our study suggests that using a composite assessment of MSKH in addition to already available tools such as FRAX® may improve identification of individuals at high fracture risk. Additional analyses are necessary to examine whether this approach can better distinguish between those who will fracture and who will not and whether the results can be reproduced in women. Disclosure of Interest None declared

OBJECTIVES: Phenotypes differ between late and early-onset systemic lupus erythematosus (SLE). Prior studies suggested that there may be more pulmonary disease among late-onset patients. Our objective was to perform a systematic review and meta-analysis to evaluate the differences in pulmonary manifestations in late- versus early-onset SLE. METHODS: We searched the literature using PubMed, CINAHL, Web of Science, Cochrane Library, and EMBASE. We excluded studies that did not include American College of Rheumatology SLE classification criteria, an early-onset SLE comparison group, or those that defined late-onset SLE as

In this study, the area under the curve was highest when using the lowest vertebral body T-score to diagnose osteoporosis. In men for whom hip imaging is not possible, the lowest vertebral body T-score improves the ability to diagnose osteoporosis in men who are likely to have an incident fragility fracture. Spine T-scores have limited ability to predict fragility fracture. We hypothesized that using lowest vertebral body T-score to diagnose osteoporosis would better predict fracture. Among men enrolled in the Osteoporotic Fractures in Men Study, we identified cases with incident clinical fracture (n = 484) and controls without fracture (n = 1,516). We analyzed the lumbar spine bone mineral density (BMD) in cases and controls (n = 2,000) to record the L1–L4 (referent), the lowest vertebral body, and International Society for Clinical Densitometry (ISCD)-determined T-scores using a male normative database and the L1–L4 T-score using a female normative database. We compared the ability of method to diagnose osteoporosis and, therefore, to predict incident clinical fragility fracture, using area under the receiver operator curves (AUCs) and the net reclassification index (NCI) as measures of diagnostic accuracy. ISCD-determined T-scores were determined in only 60 % of participants (n = 1,205). Among 1,205 men, the AUC to predict incident clinical fracture was 0.546 for L1–L4 male, 0.542 for the L1–L4 female, 0.585 for lowest vertebral body, and 0.559 for ISCD-determined T-score. The lowest vertebral body AUC was the only method significantly different from the referent method (p = 0.002). Likewise, a diagnosis of osteoporosis based on the lowest vertebral body T-score demonstrated a significantly better net reclassification index (NRI) than the referent method (net NRI +0.077, p = 0.005). By contrast, the net NRI for other methods of analysis did not differ from the referent method. Our study suggests that in men, the lowest vertebral body T-score is an acceptable method by which to estimate fracture risk.

Reduced calcium absorption is a risk factor for osteoporosis. This study examined factors associated with fractional calcium absorption (FCA) and net calcium absorption in postmenopausal women in a post hoc analysis of three completed dual-isotope studies. Data were analyzed from 50 postmenopausal women undergoing 121 inpatient research visits in three studies evaluating changes in FCA related to correction of vitamin D insufficiency (n=19), use of proton pump inhibitors (n=21), and use of aromatase inhibitors to treat breast cancer (n=10). Net calcium absorption was the product of FCA and total calcium intake in milligrams per day. Variables included subjects' age, race, body mass index, serum calcium, creatinine, parathyroid hormone, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and habitual intake of kilocalories, protein, fat, carbohydrate, fiber, calcium, iron, magnesium, oxalate, phosphorus, potassium, and vitamin D based on outpatient diet diaries. In multivariate models, subjects' age, dietary intake of kilocalories, carbohydrates, fat, fiber, calcium, and potassium were significant predictors of FCA. In multiple variable models predicting net calcium absorption, dietary intake of kilocalories, fat, fiber, calcium, potassium, and serum 1,25-dihydroxyvitamin D were significant. The square of the correlation between actual and predicted values (an approximation of R 2 ) was 0.748 for FCA and 0.726 for net calcium absorption. Similar to other studies, this study found that age, 1,25-dihydroxyvitamin D, and dietary calcium and fat were associated with calcium absorption. Dietary intake of kilocalories, carbohydrates, and potassium were new factors that were significantly associated with FCA and net calcium absorption. In summary, the study suggests that several dietary habits play a role in calcium absorption, beyond vitamin D and calcium.

Studies suggest a link between magnesium status and osteoporosis. One barrier to more conclusive research on the potential relation is measuring intestinal magnesium absorption (MgA), which requires the use of stable isotopes and a ≥6-d stool or 3-d urine collection. We evaluated alternative methods of measuring MgA. We administered 2 stable magnesium isotopes to 15 postmenopausal women (cohort 1) aged 62 ± 8 y with a dietary magnesium intake of 345 ± 72 mg/d. Participants fasted from 1200 h to 0700 h and then consumed breakfast with ∼23 mg of oral ²⁶Mg and ∼11 mg of i.v. ²⁵Mg. We measured magnesium isotope concentrations in 72-h urine, spot urine (36, 48, 60, and 72 h), and spot serum (1, 3, and 5 h) samples collected after isotope dosing. We calculated MgA using the dose-corrected fraction of isotope concentrations from the 72-h urine collection. We validated new methods in 10 postmenopausal women (cohort 2) aged 59 ± 5 y with a dietary magnesium intake of 325 ± 122 mg/d. In cohort 1, MgA based on the 72-h urine collection was 0.28 ± 0.08. The 72-h MgA correlated most highly with 0-24 h urine MgA value alone (ρ = 0.95, P < 0.001) or the mean of the 0-24 h urine and the 3-h (ρ = 0.93, P < 0.001) or 5-h (ρ = 0.96, P < 0.001) serum MgA values. In cohort 2, Bland-Altman bias was lowest (-0.003, P = 0.82) using means of the 0-24 h urine and 3-h serum MgA values. We conclude that means of 0-24 h urine and 3-h serum MgA provide a reasonable estimate of 72-h MgA. However, if researchers seek to identify small changes in MgA, we recommend a 3-d urine or extended stool collection.

Temporal and spatial variations in bone marrow adipose tissue (MAT) can be indicative of several pathologies and confound current methods of assessing immediate changes in bone mineral remodeling. We present a novel dual-energy computed tomography (DECT) method to monitor MAT and marrow-corrected volumetric BMD (mcvBMD) throughout the body. Twenty-three cancellous skeletal sites in 20 adult female cadavers aged 40–80 years old were measured using DECT (80 and 140 kVp). vBMD was simultaneous recorded using QCT. MAT was further sampled using MRI. Thirteen lumbar vertebrae were then excised from the MRI-imaged donors and examined by microCT. After MAT correction throughout the skeleton, significant differences (p

Background & Aims Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. Methods We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n = 30). Results Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. Conclusions In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293

Some patients experience reduced bone mineral density (BMD) despite bisphosphonate therapy. We performed a retrospective chart review study to detect factors associated with decreased BMD in men prescribed alendronate. Two investigators reviewed eligible medical records and used a standardized form to record potential characteristics predicting men's response to alendronate. We analyzed patient characteristics associated with annualized change in hip and spine BMD (D-BMD). Among 115 eligible men, 19 (17 %) experienced significantly decreased BMD at the hip or spine, defined as a change exceeding precision error. Eleven men (10 %) fractured during therapy. Spine D-BMD was positively associated with adherence to alendronate (R = 0.23, p = 0.02) and inversely associated with baseline body weight (R = -0.21, p = 0.03). Hip D-BMD was positively associated with annualized weight change (R = 0.19, p = 0.0498) and negatively associated with patient age and number of concomitant medications (R = -0.21, p = 0.03; R = -0.20, p = 0.03, respectively). In stepwise linear models, spine D-BMD was associated positively with alendronate adherence and multivitamin use and negatively with baseline body weight. Hip D-BMD was negatively associated with age. Fracture during treatment was associated with fracture prior to therapy (p = 0.03). In this small study of men prescribed alendronate, BMD response showed a positive association with adherence to therapy, weight gain, and use of a multivitamin. By contrast, older age, higher baseline body weight, and higher number of medications were each associated with a decrease in BMD. Larger studies are needed to confirm and extend these findings.

To investigate the effect of aromatase inhibitors (AI) on intestinal calcium absorption, measured using the gold-standard dual stable calcium isotope method. In this pilot study, we recruited 10 postmenopausal women with hormone receptor-positive breast cancer who planned to initiate AI therapy; women receiving chemotherapy were excluded. Women completed two 24 h inpatient calcium absorption study visits, the first prior to AI therapy and the second at least 6 weeks following onset of AI therapy. We calculated total fractional calcium absorption (TFCA) using the dose-corrected fractional recovery of two stable isotopes from 24 h urine collections. Ten postmenopausal women (mean ± SD age, 66 ± 7 years; 25(OH)D 40 ± 7 ng/mL, and total calcium intake of 1,714 ± 640 mg/day) exhibited no change in TFCA related to AI therapy (0.155 ± 0.042 prior to and 0.160 ± 0.064 following AI therapy, p = 1.0). Subjects exhibited a surprisingly small decline in serum estradiol levels with AI therapy that was not statistically significant. However, there was a significant correlation between duration of AI therapy and the decline in serum estradiol levels (r = −0.65, p = 0.040). In this pilot study, AI therapy did not decrease TFCA. Women with early stage breast cancer exhibited an unexpectedly low TFCA, most likely due to their high calcium intake. The null effect of AI therapy on TFCA might relate to the brief duration of AI therapy, the minimal effect of AI therapy on estradiol levels, subjects’ high calcium intake or excellent vitamin D status.

Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis. We hypothesized that alendronate plus vitamin D3 (ALN + D) would increase fractional calcium absorption (FCA). In this randomized, double-blind, placebo-controlled multicenter clinical trial, 56 postmenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations of 25 ng/mL or less and low bone mineral density (BMD) received 5 weekly doses of placebo or alendronate 70 mg plus vitamin D3 2800 IU (ALN + D). Calcium intake was stabilized to approximately 1200 mg/d prior to randomization. FCA was determined using a dual-tracer stable-calcium isotope method. FCA and 25(OH)D were similar between treatment groups at baseline (0.31 ± 0.12 ng/mL and 19.8 ± 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN + D experienced a significant least squares (LS) mean [95% confidence interval (CI)] increase in FCA [0.070 (0.042, 0.098)], whereas FCA did not change significantly in the placebo group [−0.016 (−0.044, 0.012)]. After ALN + D treatment, patients had higher 25(OH)D levels (LS mean difference 7.3 ng/mL, p

Clinicians can diagnose high urine calcium by asking patients to collect urine for 24 h or to provide a random urine specimen. In this study, random urine calcium levels were not as accurate as those from the 24-h collection. Clinicians should only use 24-h collections to diagnose high urine calcium.Clinicians diagnose hypercalciuria using a 24-h urine calcium (24HUC) or a spot urine-calcium-to-creatinine ratio (SUCCR) specimen. The SUCCR is reportedly interchangeable with the 24HUC. However, studies to date show mixed results when comparing SUCCR and 24HUC values. We systematically compared fasting and postprandial SUCCR measurements to 24HUC measurements using Bland-Altman analysis.Twenty-one postmenopausal women aged 58 ± 7 years came to the research ward for three 24-h inpatient stays. At each study visit, research nurses collected fasting morning (n = 62) and postprandial (n = 62) spot urine specimens along with carefully timed and complete 24-h urine specimens (n = 63) from each woman.Hypercalciuria was present in 13 24HUC samples (21%) using an upper limit of 250 mg/24-h. The fasting SUCCR underestimated the 24HUC (Bland-Altman bias -71 mg/24-h), with a sensitivity and specificity for diagnosing hypercalciuria of 0% and 98%, respectively. The postprandial SUCCR overestimated the 24HUC (Bland-Altman bias +61 mg/24-h), with a sensitivity and specificity of 77% and 61%, respectively. The average of fasting and postprandial SUCCR measurements had a lower Bland-Altman bias of -3 mg/24-h but demonstrated a sensitivity and specificity of only 42% and 78%, respectively.The SUCCR is not interchangeable with the 24HUC. The fasting SUCCR systematically underestimates, and the postprandial SUCCR systematically overestimates, 24HUC. The average SUCCR demonstrates low sensitivity and specificity for hypercalciuria. Clinicians must use the 24HUC to diagnose hypercalciuria in postmenopausal women.

Proton pump inhibitors (PPIs) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption (FCA). Existing studies provide conflicting information regarding the direct effects of PPIs on FCA. We evaluated the effect of PPI therapy on FCA. We recruited women at least 5 years past menopause who were not taking acid suppressants. Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method. Two FCA studies were performed 1 month apart to establish baseline calcium absorption. The third study occurred after taking omeprazole (40 mg/day) for 30 days. Each participant consumed the same foods during all FCA studies; study meals replicated subjects' dietary habits based on 7-day diet diaries. Twenty-one postmenopausal women ages 58 ± 7 years (mean ± SD) completed all study visits. Seventeen women were white, and 2 each were black and Hispanic. FCA (mean ± SD) was 20% ± 10% at visit 1, 18% ± 10% at visit 2, and 23% ± 10% following 30 ± 3 days of daily omeprazole (p = .07, ANOVA). Multiple linear regression revealed that age, gastric pH, serum omeprazole levels, adherence to omeprazole, and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3. The 1,25-dihydroxyvitamin D3 level at visit 2 was the only variable (p = .049) associated with the change in FCA between visits 2 and 3. PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use. Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture. © 2010 American Society for Bone and Mineral Research.

To evaluate, in a posthoc analysis of a previous study, whether vitamin D repletion in postmenopausal women with insufficient vitamin D increases urinary calcium excretion, as vitamin D therapy might contribute to hypercalciuria and calcium stones in susceptible individuals, and the effect of vitamin D on the risk of urolithiasis warrants attention.We recruited 18 women ator =5 years after menopause who had vitamin D insufficiency (serum 25(OH)-vitamin D, 16-24 mg/dL). We excluded women with a history of urolithiasis and kidney disease. Women had one calcium absorption study when vitamin D-insufficient, received vitamin D therapy, and completed a second calcium absorption study when vitamin D-replete. We fed subjects meals that mirrored the nutrient composition from self-reported 7-day diet diaries. To measure calcium absorption, we collected urine for 24 h during both visits.We achieved vitamin D repletion in all women (25(OH)-vitamin D before and after treatment, 22 and 63 mg/dL, respectively; P0.001). The mean calcium intake was 832 mg/day. Residual urine specimens were available for 16 women, allowing a measurement of 24-h urinary calcium. Calcium excretion did not change after vitamin D therapy (212 before vs 195 mg/day after; P = 0.60). Of four women with hypercalciuria (247 mg/day), calcium excretion decreased in three (377-312 mg/day, not significant).Vitamin D supplementation did not increase the urinary calcium excretion in healthy postmenopausal women. Many stone formers are at risk of premature bone loss, vitamin D insufficiency, or both. Based on the present results we suggest a study of patients with hypercalciuria and nephrolithiasis to determine the risks of vitamin D therapy.

ObjectiveWe hypothesized that young adults would commonly have vitamin D deficiency and that a questionnaire could help identify subjects with the condition.DesignBetween January and May 2004, we administered a questionnaire to a convenience sample of young adults. We measured each participant’s serum level of 25-hydroxyvitamin D (25(OH)D) using a chemiluminescent assay and defined deficiency as serum 25(OH)D < 16 ng/ml.Setting and subjectsWe recruited young adults living in Madison, Wisconsin without pre-existing conditions affecting vitamin D and/or Ca metabolism.ResultsOne hundred and eighty-four adults (mean age 24 years, 53 % women, 90 % Caucasian) participated in the study. Nearly three in four adults (71 %) had 25(OH)D level P = 0·004), tanning booth use (OR = 0·09, 95 % CI 0·02, 0·43, P = 0·002) and daily ingestion of two or more servings of milk (OR = 0·21, 95 % CI 0·09, 0·48, P < 0·001) were less likely to be deficient. These three questions provided a sensitivity and specificity of 79 % and 78 %, respectively, for the presence of deficiency.ConclusionsThe questionnaire is moderately useful to identify young adults likely to be vitamin D-deficient. Additional revisions of the questionnaire may improve its ability to predict vitamin D deficiency.

Vitamin D insufficiency (VDI) is widely reported. In patients with normal PTH, the diagnosis rests on increases in fractional calcium absorption (FCA) when 25(OH)D increases above 30 ng/ml. However, estimates of increased FCA after correction of VDI vary dramatically, depending on study methods. We used a dual stable calcium isotope to clarify the impact of vitamin D repletion on FCA in postmenopausal women with VDI. We hypothesized that FCA would increase with vitamin D repletion. We studied postmenopausal women with VDI [25(OH)D = 16-24 ng/ml] and an estimated calcium intakeor=1100 mg daily. Exclusion criteria included hypercalcemia, hypercalciuria, renal insufficiency, nephrolithiasis, gastrointestinal disorders, osteomalacia, prior adult fragility fracture, baseline T-score-3.0, and use of medications known to interfere with vitamin D or calcium metabolism. Each woman underwent inpatient FCA studies before and after correction of VDI. We used ergocalciferol 50,000 IU/d for 15 days to achieve vitamin D repletion. During each study, women consumed their typical diet. They ingested (44)Ca orally with breakfast and received (42)Ca intravenously. We collected urine for 24 h and measured its calcium isotope content by mass spectrometry. Eighteen women completed the study; all but two had normal PTH. During the first and second FCA studies, their mean 25(OH)D level was 22 +/- 4 and 64 +/- 21 ng/ml, respectively (p0.001). Subjects' average FCA was 24 +/- 7% initially and 27 +/- 6% after vitamin D repletion (p = 0.04). Thus, FCA increased by 3 +/- 1% with correction of VDI. Postmenopausal women with VDI experience small FCA increments with vitamin D therapy. In existing literature, this small change in FCA does not associate with lower fracture rates or consistently higher bone mass. Future studies should ascertain whether small FCA increments favorably affect the skeleton.

Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24–38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18–25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice.

Background Low fractional calcium absorption (FCA) contributes to osteoporosis but is not measured clinically, as the gold-standard method requires administration of two calcium tracers and a subsequent 24-h urine collection. We evaluated alternate methods to measure FCA, compared to the gold standard method. Methods We administered two stable calcium isotope tracers (~8 mg oral 44Ca and ~3 mg intravenous 42Ca) with breakfast to 20 fasting post-menopausal women (Cohort 1) 59 ± 7 years old with vitamin D insufficiency. We measured subsequent calcium isotope concentrations in 24-h urine samples and serum collected 1, 3 and 5 h post tracer administration during an inpatient research stay. We assessed the candidate serum estimates in a second cohort of 9 women with similar characteristics. Methods of measuring FCA were compared using correlation coefficients and Bland-Altman tests. Results FCA estimated from a 3-h serum sample correlated highest with the levels from the 24-h urine collection (ρ 0.78, p

In this study, we hypothesized that use of the lowest T-score among four lumbar vertebral bodies would lessen the impact of degenerative arthritis and other artifacts on diagnostic categorization at this site and increase study sensitivity, classifying more men with prior fracture as osteoporotic than the other two methods of lumbar spine analysis. Bone density studies of 533 male veterans measured between January and October 2002 were reviewed to determine diagnostic classification using the L1–L4 average, International Society for Clinical Densitometry (ISCD)-determined, and lowest lumbar vertebral body T-score. We calculated sensitivity and specificity of the three methods of spine analysis, using spine osteoporosis to indicate a positive test and prior fracture as the true indicator of osteoporosis. The lowest lumbar T-score performed with similar sensitivity and specificity to that of the lowest hip or wrist T-score in the ability to classify men with prior fracture as osteoporotic, whereas the average L1–L4 and ISCD-determined T-scores performed with lower sensitivity, but better specificity. In conclusion, this retrospective study suggests that use of the lowest vertebral body T-score among men increases diagnostic sensitivity of lumbar spine bone mass measurement. Prospective studies are needed to determine which of these three methods of lumbar spine analysis best predicts future fragility fracture in men and women.