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.

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.

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.

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.

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.

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.

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.

Pathophysiology of growth hormone secretion disorders and their impact on bone microstructure as measured by trabecular bone score.

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin.

This analysis was performed in Zambian children who had a high prevalence of hypervitaminosis A, defined as > 1.0 µmol retinol/g liver. Bone parameters included markers of bone formation (P1NP), bone resorption (CTX), parathyroid hormone, calcium, vitamin A, and vitamin D. Low dietary vitamin A intake increased P1NP. PURPOSE: Vitamin A (VA) interacts with bone health, but mechanisms require clarification. In countries where multiple interventions exist to eradicate VA deficiency, some groups are consuming excessive VA. Bone metabolism and inflammatory parameters were measured in Zambian children who had high prevalence of hypervitaminosis A determined by 13C-retinol isotope dilution. METHODS: Children (n = 143), 5 to 7 years, were recruited into a placebo-controlled biofortified orange maize feeding study for 90 days. Bone turnover (P1NP and CTX) and inflammatory (C-reactive protein (CRP) and alpha-1-acid glycoprotein) biomarkers were measured in fasting blood samples before and/or after intervention with the following: (1) VA at the recommended dietary allowance (400 µg retinol activity equivalents/day (as retinyl palmitate)), (2) maize enhanced with the provitamin A carotenoid ß-carotene (2.86 mg/day), or (3) a placebo. Parathyroid hormone, calcium, and 25(OH)-vitamin D were measured at end line. RESULTS: Bone formation, as measured by P1NP, increased (P < 0.0001) in the placebo group who consumed low preformed VA during the intervention. Bone resorption, measured by CTX, was not affected. P1NP and CTX were negatively associated with inflammation, most strongly with CRP. Serum calcium did not differ among groups and was low (7.29 ± 0.87 µg/dL). Serum 25(OH) D did not differ among groups (54.5 ± 15 nmol/L), with 91% < 75 nmol/L and 38% < 50 nmol/L. CONCLUSIONS: Reduction of dietary preformed VA in Zambian children for 4 months improved bone formation. Chronic consumption of preformed VA caused hypervitaminosis A and may impair bone formation. In children, this could be associated with failure to accrue optimal peak bone mass. TRIAL REGISTRATION: The NIH Clinical Trial registry number is NCT01814891; https://clinicaltrials.gov/ct2/show/NCT01814891 .

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 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 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.

Effect of vertebral exclusion on TBS and FRAX calculations.

Degenerative changes falsely elevate BMD; however, their impact on TBS is unclear. This study examined how spinal degenerative changes affect TBS-adjusted fracture risk (FRAX). In a majority, but not all patients in this sample, TBS decreased after exclusion of vertebrae with degenerative change. Therefore, vertebral exclusion for TBS is suggested. INTRODUCTION: Spinal degenerative changes elevate DXA-measured BMD, but reports find trabecular bone score (TBS) relatively unaffected. However, we observed patients where degenerative changes elevated both. Consequently, this study explored whether vertebral exclusion impacts TBS and subsequently TBS-adjusted FRAX risk. METHODS: Clinical DXA interpretations of one physician were reviewed; those with vertebrae excluded per ISCD guidance were included in this study. BMD and TBS at L1-4 and from post-exclusion vertebrae were collected and used to adjust fracture risk (FRAX). RESULTS: Of the patients, 102 had vertebrae excluded; their mean (SD) age, BMI, and lowest T-score were 71.6 (9.5) years, 25.4 (4.5) kg/m2, and - 2.8 (1.0), respectively. Compared to L1-4, vertebral exclusion lowered (p < 0.0001) mean spine BMD and TBS by 9.5 and 3.1%, respectively. Vertebral exclusion decreased TBS by 0.040, being lower in 83%. In those with lower TBS, the mean adjusted 10-year fracture risk increased (p < 0.0001) by 0.94 and 0.32% for major osteoporotic (MOF) and hip fracture, respectively, in some risk increased by up to 4%. In those with higher TBS, adjusted risk was reduced, MOF - 0.49% and hip - 0.1%. CONCLUSION: Vertebral exclusion following ISCD recommendations generally, but not always, lowers TBS. Consequently, the impact on TBS adjusted FRAX risk is variable. In most patients, vertebral exclusion lowers TBS; in some, this could result in a relevant change in calculated fracture risk. It seems reasonable to use TBS values from evaluable vertebrae to adjust FRAX. Further research to determine if vertebral exclusion improves fracture risk prediction is needed.