Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

Should vertebral fracture assessment be performed in Fracture Liaison Service patients with non-vertebral fracture?

Prior non-vertebral fractures, except of the ankle, are associated with increased likelihood of vertebral fracture. As knowledge of vertebral fracture presence may alter care, vertebral fracture assessment (VFA) is indicated in patients with prior fracture. INTRODUCTION: Vertebral fractures are often unappreciated. It was recently advocated that all Fracture Liaison Service (FLS) patients have densitometric VFA performed. We evaluated the likelihood of vertebral fracture identification with VFA in patients with prior fracture using the Manitoba Bone Density database. METHODS : VFA was performed in patients with T-scores below - 1.5 and age 70 + (or younger with height loss or glucocorticoid use) obtaining bone densitometry in Manitoba from 2010 to 2018. Those with prior clinical vertebral fracture, pathologic fracture, or uninterpretable VFA were excluded. Vertebral fractures were identified using the modified ABQ method. Health records were assessed for non-vertebral fracture (excluding head, neck, hand, foot) diagnosis codes unassociated with trauma prior to DXA. Multivariable odds ratios (ORs) for vertebral fracture were estimated without and with adjustment for age, sex, body mass index, ethnicity, area of residence, income level, comorbidity score, diabetes mellitus, falls in the last year, glucocorticoid use, and lowest BMD T-score. RESULTS: The study cohort consisted of 12,756 patients (94.4% women) with mean (SD) age 75.9 (6.8) years. Vertebral fractures were identified in 1925 (15.1%) overall. Vertebral fractures were significantly more likely (descending order) in those with prior pelvis, hip, humerus, other sites, and forearm, but not ankle fracture. There was modest attenuation with covariate adjustment but statistical significance was maintained. CONCLUSIONS: Prior hip, humerus, pelvis, forearm, and other fractures are associated with an increased likelihood of previously undiagnosed vertebral fracture, information useful for risk stratification and monitoring. These data support recommending VFA in FLS patients who are age 70 + with low BMD.

Opportunistic Use of Lumbar Magnetic Resonance Imaging for Osteoporosis Screening.

Magnetic resonance imaging (MRI) is a routine assessment before spine surgery. We found that the opportunistic use of MRI with the vertebral bone quality (VBQ) score has good diagnostic ability, with a threshold value of VBQ > 3.0, in recognizing patients who may need further osteoporosis evaluation. INTRODUCTION: The purpose of this study was to determine whether the opportunistic use of magnetic resonance imaging (MRI) is useful for identifying spine surgical patients who need further osteoporosis evaluation. METHODS: This retrospective study evaluated 83 thoracolumbar spine surgery patients age ≥ 50 who received T1-weighted MRI. Opportunistic MRI was evaluated with the vertebral bone quality (VBQ) score, VBQ (fat) score, and signal-to-noise ratio (SNR). Each uses the median L1-L4 vertebral body signal intensities (SI) divided by either the L3 cerebrospinal fluid (CSF) SI, average SI of the L1 and S1 dorsal fat, or standard deviation (SD) of the background SI dorsal to the skin. Single-level VBQ was calculated as the ratio of the L1 vertebral body and L1 CSF SIs. Receiver-operator curve analysis was performed to determine diagnostic ability. RESULTS: The mean age was 70.10, 80% were female, and 96% were Caucasian. The mean ± SD VBQ, single-level VBQ, VBQ (fat), and SNR were 3.39 ± 0.68, 3.56 ± 0.81, 3.95 ± 1.89, and 113.18 ± 77.26, respectively. Using area under the curve, the diagnostic ability of VBQ, single-level VBQ, VBQ (fat), and SNR for clinical osteoporosis were 0.806, 0.779, 0.608, and 0.586, respectively. Diagnostic threshold values identified with optimal sensitivity and specificity were VBQ of 2.95 and single-level VBQ of 3.06. CONCLUSION: Opportunistic use of MRI is a simple, effective tool that may help recognize patients who are at risk for complications related to bone disease. A VBQ > 3.0 can identify patients who need additional diagnostic evaluation.

Effect of degeneration on bone mineral density, trabecular bone score and CT Hounsfield unit measurements in a spine surgery patient population.

This study investigated the impact of spinal degeneration on bone mineral density (BMD), trabecular bone score (TBS), and CT Hounsfield units in an at-risk population. We found that BMD was increased by degeneration, whereas TBS and HU were unaffected. These findings support that TBS is not adversely affected by spinal degeneration. INTRODUCTION: This study evaluated the impact of spinal degeneration on BMD and TBS measured by dual-energy x-ray absorptiometry (DXA) and on CT HU in a spine surgery patient population. METHODS: A retrospective study of 63 patients referred for consideration of spine surgery or with history of spine surgery was performed. Patients were included if a DXA scan and a CT containing the lumbar spine were obtained within 18 months of each other. DXA data were collected and analyzed by vertebral level. Individual vertebrae were assessed for degenerative changes by qualitative evaluation of the anterior and posterior elements using CT. Degeneration scores were compared to BMD T-scores, TBS and CT HU at individual vertebral levels L1-4, and after applying International Society for Clinical Densitometry (ISCD) criteria for excluding vertebrae from diagnostic consideration. RESULTS: Mean patient age and BMI were 67.2 years and 27.8 kg/m2, respectively; 79.4% were female. Mean (SD) lowest T-scores of the hip, spine, and lowest overall T-score were - 1.3 (1.4), - 1.7 (0.9), and - 1.9 (1.0), respectively. Osteoporosis was present by T-score in 38% and osteopenia in 52%; 10% had a history of osteoporotic fracture. The mean degeneration score of individual vertebrae was 4.1 on a 0-6 scale. T-score correlated moderately with degeneration score (Spearman's rho 0.484, p < 0.001), whereas TBS and HU were unrelated. ISCD excluded vertebrae had a higher degeneration score than included vertebrae (p = < 0.001). CONCLUSIONS: In a spine surgery population, TBS and CT HU values are unrelated to degeneration score and thus appear unaffected by lumbar vertebral degenerative changes. Additionally, these data support the ISCD criteria for vertebral exclusion.

Defining an international cut-off of two-legged countermovement jump power for sarcopenia and dysmobility syndrome.

We aimed to establish jump power cut-offs for the composite outcome of either sarcopenia (EWGSOP2) or dysmobility syndrome using Asian and Caucasian cohorts. Estimated cut-offs were sex specific (women: < 19.0 W/kg; men: < 23.8 W/kg) but not ethnicity specific. Jump power has potential to be used in definitions of poor musculoskeletal health. PURPOSE: Weight-corrected jump power measured during a countermovement jump may be a useful tool to identify individuals with poor musculoskeletal health, but no cut-off values exist. We aimed to establish jump power cut-offs for detecting individuals with either sarcopenia or dysmobility syndrome. METHODS: Age- and sex-matched community-dwelling older adults from two cohorts (University of Wisconsin-Madison [UW], Korean Urban Rural Elderly cohort [KURE], 1:2) were analyzed. Jump power cut-offs for the composite outcome of either sarcopenia defined by EWGSOP2 or dysmobility syndrome were determined. RESULTS: The UW (n = 95) and KURE (n = 190) cohorts were similar in age (mean 75 years) and sex distribution (68% women). Jump power was similar between KURE and UW women (19.7 vs. 18.6 W/kg, p = 0.096) and slightly higher in KURE than UW in men (26.9 vs. 24.8 W/kg, p = 0.050). In UW and KURE, the prevalence of sarcopenia (7.4% in both), dysmobility syndrome (31.6% and 27.9%), or composite of either sarcopenia or dysmobility syndrome (32.6% and 28.4%) were comparable. Low jump power cut-offs for the composite outcome differed by sex but not by ethnicity (< 19.0 W/kg in women; < 23.8 W/kg in men). Low jump power was associated with elevated odds of sarcopenia (adjusted odds ratio [aOR] 4.07), dysmobility syndrome (aOR 4.32), or the composite of sarcopenia or dysmobility syndrome (aOR 4.67, p < 0.01 for all) independent of age, sex, height, and ethnicity. CONCLUSION: Sex-specific jump power cut-offs were found to detect the presence of either sarcopenia or dysmobility syndrome in older adults independent of Asian or Caucasian ethnicity.

Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis.

Odanacatib (ODN) was investigated as an osteoporosis treatment in 292 men. Compared with placebo, odanacatib improved bone mineral density and led to sustained bone resorption decreases while producing relatively little bone formation reduction that leveled off with time. However, increased risk of stroke in another study stopped further odanacatib development. INTRODUCTION: ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. METHODS: Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ - 2.5 to ≥ - 4.0 without prior vertebral fracture or ≤ - 1.5 to ≥ - 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50 mg or placebo. All received 5600 IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200 mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. RESULTS: Overall, 292 men, mean age 68.8 years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3 months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. CONCLUSION: Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT01120600 (registered May 11, 2010).

An Exploratory Study of the Texture Research Investigational Platform (TRIP) to Evaluate Bone Texture Score of Distal Femur DXA Scans - A TBS-Based Approach.

Poor bone status is associated with increased complications following orthopedic surgery. Therefore, assessing site-specific skeletal status prior to or after orthopedic surgery to optimize outcomes is appealing. The trabecular bone score (TBS) approach, a surrogate for microarchitecture, was adapted to the Texture Research Investigational Platform (TRIP), which allows assessment of many skeletal sites imaged by various modalities. TRIP generates a bone texture score (TBS ORTHO), which could potentially guide surgical decision-making and offer insight into postsurgical fracture risk. As distal femur bone loss occurs following total knee arthroplasty (TKA), we hypothesized that TBS ORTHO after TKA would identify poorer texture in the operated femur compared to the nonoperated. We evaluated 30 subjects (15 M/15 F) with unilateral TKA 2-5 yr previously, mean age 67.9 yr and body mass index 30 kg/m2. Using a Lunar iDXA, lumbar spine and entire femur scans were obtained, the latter using the atypical femur fracture feature. Distal femur bone mineral density (BMD) and TBS ORTHO were obtained using manual regions of interest (ROI) at 15% and 25% of leg length from the intercondylar notch. TBS ORTHO was determined using distal femur DICOM images and TRIP v1.0 (Medimaps, France). Differences in operated vs nonoperated femur were evaluated by paired t test. As previously reported, operated leg BMD was approx 10% lower at 15% and 25% ROIs. Similarly, TBS ORTHO values in the operated leg were approx 5% lower (p < 0.05) at these same ROIs. Distal femur TBS ORTHO and BMD were largely unrelated. TBS ORTHO reproducibility at these ROIs was approx 3.5%. In conclusion, this pilot study documents the feasibility of reproducibly obtaining distal femur TBS ORTHO values. Lower values were observed in the surgical leg, consistent with the bone loss that follows TKA. Further work is indicated to refine TRIP use and evaluate whether such data provides guidance for surgical decision-making and improves periprosthetic fracture prediction.

Targeted bone density testing for optimizing fracture prevention in Canada.

The Canadian FRAX® tool used without bone mineral density (BMD) is highly sensitive for identifying individuals qualifying for pharmacotherapy based upon an intervention threshold of 20% for major osteoporotic fracture risk (MOF) computed with BMD. INTRODUCTION: This analysis was performed to inform initial BMD testing as part of Osteoporosis Canada's Guidelines Update for women and men at average risk, assuming a pharmacotherapy intervention threshold of 20% for FRAX® MOF computed with BMD. METHODS: Women and men age 50 + without previous low-trauma fracture or high-risk medication use were identified in a BMD registry for the province of Manitoba, Canada. Fracture probability assessments with the Canadian FRAX® tool were computed without and with BMD (denoted MOF-clinical and MOF-BMD, respectively). RESULTS: The study population consisted of 50,700 women (mean age 65.5 ± 9.4 years) and 4152 men (69.2 ± 10.0 years). FRAX MOF-clinical score was > 10% in 33.8% of women and 13.3% of men (P < 0.001). The median (interquartile range [IQR]) age for MOF-clinical to reach 10% in women was 70 (69-72) and 65 years (62-67) years in the absence and presence of additional FRAX clinical risk factors, respectively. In men, comparable ages were 83 years [82-86] and 76 [70-78] years. Using MOF-BMD of 20% as the intervention threshold, 4.3% of women and 0.7% of men qualified for treatment. MOF-clinical > 10% had high sensitivity to identify those qualifying for treatment (99.3% in women and 99.1% in men). An age-based rule ("BMD testing is indicated at age 70 if no additional FRAX clinical risk factors are present, or at age 65 if one or more clinical risk factors exists") gave similarly high sensitivity (women 99.9% and men > 99.9%). CONCLUSIONS: FRAX without BMD offers an effective strategy to identify individuals meeting the current Canadian treatment threshold based upon FRAX® with BMD (≥ 20%). Moreover, this can be operationalized using simple age cutoffs of 70 years in the absence of additional clinical risk factors and 65 years in the presence of additional clinical risk factors.

Frequency of normal bone measurement in postmenopausal women with fracture: a registry-based cohort study.

This registry-based cohort study assessed the percentage of women with prior or incident fracture who had normal bone defined as a normal bone mineral density T-score and normal trabecular bone score (TBS). Inclusion of TBS reduced the percentage with normal bone. Normal bone measurement is rare in women with fracture. INTRODUCTION: Some fractures occur in women with normal BMD. We hypothesized that adding trabecular bone score (TBS) to DXA would (1) demonstrate that few women with fracture have normal bone, i.e., normal BMD T-score and TBS and (2) increase the percentage of women with fracture that have abnormal bone defined as a BMD T-score ≤ - 2.5 or low TBS. METHODS: The public healthcare system in Manitoba, Canada, makes it possible to link clinical DXA data to population databases. This study included all women age 50+ with a first DXA from February 1999 to March 2018 with valid BMD, TBS, and fracture data. Bone status was defined as Normal = BMD T-score of the spine, femoral neck, and total femur ≥ - 1.0 AND TBS > 1.31; Abnormal = BMD T-score ≤ - 2.5 OR TBS < 1.23; and borderline = all others. Analyses were stratified by age decade. RESULTS: Among women with prior (n = 4649) or incident (n = 2547) fracture, bone status assessed by both BMD and TBS was normal in only 6% and 4%, respectively. In women with prior or incident hip fracture, normal bone was present in < 1%. The prevalence of normal bone declined (p trend < 0.001) with age as expected. BMD T-score osteoporosis was present in 40% with any prior and 46% with any incident fracture. BMD T-score osteoporosis was present in 65% and 60% with prior and incident hip fracture, respectively. Including TBS with BMD increased the percentage of women with abnormal bone to 61% and 68% for any prior or incident fracture and to 80% and 81% for prior or incident hip fracture, respectively (all p < 0.001). CONCLUSION: Including TBS with BMD increases identification of abnormal bone in women with fracture compared with BMD alone. Normal bone is present in < 6% of women with any fracture and < 1% of those with hip fracture. What is thought to be normal bone in women with fracture is rarely normal.

Core principles for fracture prevention: North American Consensus from the National Osteoporosis Foundation, Osteoporosis Canada, and Academia Nacional de Medicina de Mexico.

Core principles for fracture prevention address fundamental concepts for the evaluation and management of patients at risk for fracture. These are intended to form the foundation of clinical practice guidelines and represent a first step toward guideline harmonization. INTRODUCTION: The large number of clinical practice guidelines for osteoporosis and discordance of recommendations has led to confusion among clinicians and patients, and likely contributes to the large osteoporosis treatment gap. We propose that stakeholder organizations reach agreement on fundamental principles in the management of osteoporosis and prevention of fracture as a first step toward a goal of guideline harmonization. METHODS: The best available evidence, as interpreted by an ad hoc working group of expert representatives from major osteoporosis societies in North America, was considered in the development of core principles for skeletal healthcare. These principles were subsequently endorsed by the USA National Osteoporosis Foundation, Osteoporosis Canada, and Academia Nacional de Medicina de Mexico (National Academy of Medicine of Mexico). RESULTS: Core principles are summarized here in bullet format. Categories include evaluation, lifestyle and nutrition, pharmacological therapy, and monitoring. A pathway forward to achieve guideline harmonization, at least in part, is proposed. CONCLUSION: Greater concordance of recommendations for the care of patients at risk for fracture are expected to lead to improved patient care across jurisdictions, with a narrowing of the osteoporosis treatment gap and reduced burden of fractures.

Consensus statement from 2nd International Conference on Controversies in Vitamin D.

The 2nd International Conference on Controversies in Vitamin D was held in Monteriggioni (Siena), Italy, September 11-14, 2018. The aim of this meeting was to address ongoing controversies and timely topics in vitamin D research, to review available data related to these topics and controversies, to promote discussion to help resolve lingering issues and ultimately to suggest a research agenda to clarify areas of uncertainty. Several issues from the first conference, held in 2017, were revisited, such as assays used to determine serum 25-hydroxyvitamin D [25(OH)D] concentration, which remains a critical and controversial issue for defining vitamin D status. Definitions of vitamin D nutritional status (i.e. sufficiency, insufficiency and deficiency) were also revisited. New areas were reviewed, including vitamin D threshold values and how they should be defined in the context of specific diseases, sources of vitamin D and risk factors associated with vitamin D deficiency. Non-skeletal aspects related to vitamin D were also discussed, including the reproductive system, neurology, chronic kidney disease and falls. The therapeutic role of vitamin D and findings from recent clinical trials were also addressed. The topics were considered by 3 focus groups and divided into three main areas: 1) "Laboratory": assays and threshold values to define vitamin D status; 2) "Clinical": sources of vitamin D and risk factors and role of vitamin D in non-skeletal disease and 3) "Therapeutics": controversial issues on observational studies and recent randomized controlled trials. In this report, we present a summary of our findings.

DXA evaluation of femoral bone mineral density and cortical width in patients with prior total knee arthroplasty.

Periprosthetic fractures after total knee arthroplasty (TKA) have devastating consequences. Osteoporosis increases periprosthetic fracture risk, but distal femur bone mineral density (BMD) is not measured post-TKA. This study measured distal femur BMD and cortical width; both were lower in the TKA compared to the non-operated leg. BMD measurement reproducibility was good. Standardized DXA regions of interest are proposed. INTRODUCTION: Periprosthetic fractures following total knee arthroplasty (TKA) are not rare. We hypothesized that TKA is associated with low BMD, potentially increasing periprosthetic fracture risk. However, distal femur dual energy x-ray (DXA) measurement is virtually never performed after TKA due to lack of standardized approaches. Thus, this study's aims were to develop standard DXA femur regions of interest (ROIs), assess cortical width, and determine measurement reproducibility in TKA patients. METHODS: Thirty adults (15 M/15 F) age 59-80 years with unilateral, primary TKA within 2-5 years had femoral DXA scans performed in duplicate using a Lunar iDXA densitometer. In prior work, we established that femur BMD was lowest in the distal metaphysis and highest in mid-shaft. Thus, BMD and cortical width were measured at 15%, 25%, and 60% of the femur length measured from the distal notch. Femur BMD and cortical width were compared between limbs (TKA vs. non-operated side) by paired t test. RESULTS: BMD was 3.2-9.9% lower (p < 0.001) in the operated femur at all custom ROIs; substantial between individual differences existed with some up to 30% lower. Cortical width was lower (p < 0.05) at the 25% ROI on the TKA side. BMD reproducibility was excellent; CV 0.85-1.33%. CONCLUSIONS: Distal femur BMD can be reproducibly measured using DXA and is ~ 10% lower on the TKA leg. Similarly, medial and lateral cortices are thinner at the 25% ROI. These bone changes likely increase periprosthetic fracture risk. Further work to define and mitigate periprosthetic fracture risk after TKA is needed.

DXA Measured Distal Femur Bone Mineral Density in Patients After Total Knee Arthroplasty: Method Development and Reproducibility.

INTRODUCTION: Total knee arthroplasty (TKA) is increasingly being performed. Distal femur periprosthetic fracture is a potentially catastrophic complication following TKA and existing data document substantial distal femur bone mineral density (BMD) loss following TKA. However, distal femur BMD is virtually never measured clinically as no consensus approach exists. This pilot study's purpose was to define regional BMD variation throughout the femur, suggest standard dual-energy X-ray absorptiometry (DXA) regions of interest (ROIs) and evaluate BMD reproducibility at these ROIs. METHODS: Thirty volunteers 2-5 yr post TKA had both entire femurs imaged twice using a Lunar iDXA with subject repositioning between scans; the atypical femur fracture feature of enCORE software was utilized. To define femoral BMD distribution, custom 1 cm ROIs were stacked one atop the other starting at the intercondylar notch and continuing to the base of the lesser trochanter. Femur length was measured with the ruler tool to calculate distance at 5% increments. ROIs encompassing each 5% increment were utilized to measure BMD at each location. Descriptive statistics were used to determine mean BMD at each ROI and reproducibility at the 15%, 25%, 45%, 60%, and 80% ROIs. RESULTS: The 5 and 10% ROIs included prosthetic and/or patella, causing high BMD values. Distal femur BMD was lowest at the 15% ROI and was higher (p < 0.05) at each more proximal ROI to 45%, then plateaued from 45% to 75%. BMD reproducibility at these regions was excellent; coefficient of variation (CV) from ∼1% to 3.5%. As periprosthetic fractures generally occur in the distal femur, we propose measuring femur BMD using ROIs placed at 15% and 25%. A 60% region could also be used as a highly cortical site. CONCLUSION: Existing DXA capabilities allow distal femur BMD measurement with good reproducibility. Further research using standardized ROIs to assess distal femur BMD loss after TKA, and interventions to mitigate this loss, is indicated.

DXA Errors Are Common and Reduced by Use of a Reporting Template.

OBJECTIVE: High quality dual energy X-ray absorptiometry (DXA) acquisition, analysis, and reporting demands technical and interpretive excellence. We hypothesized that DXA errors are common and of such magnitude that incorrect clinical decisions might result. In this 2-phase study, we evaluated DXA technical and interpretation error rates in a clinical population and subsequently assessed if implementing an interpretation template reduced errors. METHODS: In phase 1, DXA scans of 345 osteoporosis clinic referrals were reviewed by International Society for Clinical Densitometry-certified technologists (n = 3) and physicians (n = 3). Technologists applied International Society for Clinical Densitometry performance standards to assess technical quality. Physicians assessed reporting compliance with published guidance, relevance of technical errors and determined overall and major error prevalence. Major errors were defined as "provision of inaccurate information that could potentially lead to incorrect patient care decisions." In phase 2, a DXA reporting template was implemented at 2 clinical DXA sites after which the 3 physicians reviewed 200 images and reports as above. The error prevalence was compared with the 298 patients in phase 1 from these sites. RESULTS: In phase 1, technical errors were identified in 90% of patients and affected interpretation in 13%. Interpretation errors were present in 80% of patients; 42% were major. The most common major errors were reporting incorrect information on bone mineral density change (70%) and incorrect diagnosis (22%). In phase 2, at these 2 clinical sites, major errors were present in 37% before and 17% after template implementation. Template usage reduced the odds of major error by 66% (odds ratio 0.34, 95% confidence interval 0.21, 0.53, and p < 0.0001). CONCLUSION: DXA technical and interpretation errors are extremely common and likely adversely affect patient care. Implementing a DXA reporting template reduces major errors and should become common practice. Additional interventions, such as requiring initial and ongoing training and/or certification for technologists and interpreters, are suggested.

Multiple vertebral fractures following osteoporosis treatment discontinuation: a case-report after long-term Odanacatib.

INTRODUCTION: Case reports of women sustaining multiple vertebral fractures (VF) soon afterdenosumab discontinuation are accumulating. METHODS: We report a woman with five new vertebral fractures in ~8 months following discontinuation of long-term odanacatib (ODN), an experimental cathepsin K inhibitor. RESULTS: DXA examination demonstrated an ~12% decline in bone mineral density (BMD) and ~9% decline in trabecular bone score (TBS) since ODN discontinuation. Laboratory evaluation did not reveal a secondary cause of bone loss. CONCLUSIONS: This case mimics observations following denosumab discontinuation, but, to our knowledge, is the first reported with ODN and the first documenting substantial decline in TBS. While not directly clinically relevant as ODN is no longer being developed, this case raises the possibility that a syndrome of multiple vertebral fractures could follow discontinuation of various potent osteoporosis therapies that produce major BMD increases but do not have persisting bone effects (i.e., all non-bisphosphonates). Use of antiresorptive therapies to prevent rapid bone loss following discontinuation of potent bone active agents seems appropriate. Identification of those patients who could be at risk for the multiple VF syndrome is needed.

Could bioelectric impedance spectroscopy (BIS) measured appendicular intracellular water serve as a lean mass measurement in sarcopenia definitions? A pilot study.

DXA lean mass measurement for sarcopenia diagnosis is not always possible. Bioelectric impedance spectroscopy (BIS), a portable technology, is a potential alternative to DXA-measured lean mass. This pilot study explores the possibility and proposes an arbitrarily chosen potential cut-point for appendicular intracellular water corrected by height (aICW/ht2). INTRODUCTION: Sarcopenia definitions often include DXA lean mass measurement. However, DXA is not always available. We explored the potential of a less-expensive mobile method, bioelectric impedance spectroscopy (BIS), to assess lean mass for sarcopenia determination. We hypothesized that BIS-measured appendicular intracellular water (aICW/ht2) would correlate with DXA-measured appendicular lean mass (ALM)/ht2 and with functional parameters. If so, establishing an aICW/ht2 cut-point in sarcopenia definitions may be feasible. METHODS: Sixty-one community-dwelling women, mean age 79.9, had BIS and DXA lean mass, grip strength, gait speed, and jumping mechanography assessments. BIS aICW was calculated using limb length and intracellular water resistance. aICW/ht2 was compared to DXA-measured ALM/ht2 by linear regression. The European Working Group ALM/ht2 and an exploratory aICW/ht2 cut-point were utilized. RESULTS: In this cohort, ALM/ht2 and aICW/ht2 were moderately correlated, R2 = 0.55, p < 0.0001. Lean mass was low in 7 and normal in 44 by BIS and DXA. Those with low aICW/ht2 had lower grip strength (p = 0.04) and jump power (p = 0.0002) than those with normal aICW/ht2 and ALM/ht2. Subjects with low ALM/ht2 had lower jump power (p = 0.0006) but were not different in gait speed or grip strength. CONCLUSIONS: BIS aICW is correlated with DXA-measured ALM directly, and when height adjusted. An aICW/ht2 cut-point of 6.5 L/m2 identified 70% of women with low ALM/ht2. Women with low lean mass by DXA and BIS had poorer function measured by jump power. These pilot data support further evaluation of BIS measurement inclusion into sarcopenia definitions.

Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.

DXA-measured lean mass is often used to assess muscle mass but has limitations. Thus, we compared DXA lean mass with two novel methods-bioelectric impedance spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did not measure lean mass similarly and the correlation with muscle biomarkers/function varied. INTRODUCTION: Muscle function tests predict adverse health outcomes better than lean mass measurement. This may reflect limitations of current mass measurement methods. Newer approaches, e.g., bioelectric impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle mass would better correlate with function and bone/muscle biomarkers than DXA measured lean mass. METHODS: Evaluations of muscle/lean mass, function, and serum biomarkers were obtained in older community-dwelling adults. Mass was assessed by DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump power were examined. Potential muscle/bone serum biomarkers were measured. Mass measurements were compared with functional and serum data using regression analyses; differences between techniques were determined by paired t tests. RESULTS: Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years. The lean/muscle mass assessments were correlated (.57-.88) but differed (p < 0.0001) from one another with DXA total body less head being highest at 37.8 (7.3) kg, D3-C muscle mass at 21.1 (4.6) kg, and BIS total body intracellular water at 17.4 (3.5) kg. All mass assessment methods correlated with grip strength and jump power (R = 0.35-0.63, p < 0.0002), but not with gait speed or repeat chair rise. Lean mass measures were unrelated to the serum biomarkers measured. CONCLUSIONS: These three methodologies do not similarly measure muscle/lean mass and should not be viewed as being equivalent. Functional tests assessing maximal muscle strength/power (grip strength and jump power) correlated with all mass measures whereas gait speed was not. None of the selected serum measures correlated with mass. Efforts to optimize muscle mass assessment and identify their relationships with health outcomes are needed.

Do Textiles Impact DXA Bone Density or Body Composition Results?

External artifacts can confound dual-energy X-ray absorptiometry (DXA) measurements. It is often accepted that garments free of metal do not affect DXA results; however, little data exist in this regard. It is plausible that some textiles absorb radiation and thereby alter DXA results. We hypothesized that some dense or synthetic textiles, for example, reflective materials, might alter DXA-measured bone and soft tissue mass. Hologic and GE Lunar spine phantoms and a Bioclinica prototype total body phantom were imaged on a GE Lunar iDXA and Prodigy densitometer. Each phantom was scanned 10 times to establish mean values. Subsequently, 2 layers of various fabrics were placed over the entire top surface of the phantom, and 10 scans were performed without repositioning. Samples of natural, synthetic, or embellished fabric (including those with reflective material) and of varying thickness were used. Wilcoxon signed rank tests were used to compare the means between bare phantom and textile-covered phantom. Significant differences were demonstrated often, depending on the scanner, phantom, and textile used. A polyester fabric with reflective strip consistently altered measurements. For example, this fabric increased measured mean lumbar spine bone mineral density and total body bone mineral content by 0.008 g/cm2 and 3.6 g, respectively (p < 0.01). Similarly, mean total body fat decreased (-173 g) and lean mass increased (+213 g; p < 0.01). Fat and lean mass were also affected by metallic thread, wool, blend denim, and shiny polyester (p < 0.05), and lean mass was affected by cotton denim and sweatshirt material (p < 0.0003). In conclusion, textiles can affect DXA-measured bone mineral density and body composition results. Even small amounts of reflective material could alter mass measurements by ~25% of the least significant change. Clothing made of dense textiles (e.g., wool and denim) or those with reflective material and metallic thread should be avoided during DXA scanning.

Is drug-induced bone loss acceptable in premenopausal women? A practical fracture risk modeling exercise.

Premenopausal bone loss increases fracture risk later in life. Depending on peak values, varying degrees of bone mass and microarchitectural loss can be tolerated. We suggest that risk-benefit assessments of drugs that cause premenopausal bone loss be individualized considering baseline status and subsequent BMD and TBS loss. INTRODUCTION: It is logical that drug-induced loss of bone mass and microarchitecture in young adults increase fracture risk later in life. However, no existing data quantify how drug-induced bone loss in younger adults impacts fracture risk later in life. As such, no guidance exists to address the question "How much, if any, drug-induced bone loss in premenopausal women is acceptable?" Thus, we performed a systematic fracture risk modeling exercise examining various degrees of bone loss, and estimated the impact on 10-year major osteoporosis-related fracture risk later in life. METHODS: The FRAX® tool was used in conjunction with BMD and trabecular bone score (TBS) adjustment to estimate major osteoporotic fracture probability later in life resulting from varying degrees of hypothetical premenopausal drug-induced BMD and TBS loss. The resulting 10-year fracture probabilities were assessed against the US and the UK treatment guidance to determine the amount of premenopausal BMD and TBS loss that would result in a recommendation to initiate medical treatment to reduce fracture risk later in life that would not otherwise have been recommended in the absence of premenopausal bone loss. RESULTS: For women whose peak bone mass is between the 5th and 50th percentiles, varying degrees of BMD and TBS loss could be tolerated without reaching treatment thresholds. The degree of tolerable bone loss was primarily dependent on baseline bone status. Those whose peak BMD and TBS are in the 50th percentile or above could tolerate a 10% reduction in BMD and TBS without reaching treatment thresholds by age 75, whereas those in the 5th percentile would reach treatment thresholds by age 75 with no drug-induced reduction in BMD or TBS. Women in the 25th percentile could tolerate a 4% BMD loss and 2% TBS decline without reaching treatment thresholds by age 75. CONCLUSIONS: For clinicians and regulatory bodies to assess the consequence of drug-induced premenopausal bone loss, we propose an individualized approach considering both loss of BMD and TBS in concert with baseline bone status and the resultant effect on fracture risk in later life using the assumption that such losses are irreversible.