Skeletal fluorosis: an uncommon cause, yet a rescue treatment?

PURPOSE: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases. CASE PRESENTATION: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden. CONCLUSION: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.

Periprosthetic fractures are osteoporotic fractures: missed opportunities for osteoporosis diagnosis.

Joint replacement surgery is common in older adults, leading to increasing periprosthetic fracture (PPFx) occurrence. We reviewed all PPFx seen over a 4-year period at an academic hospital. Clinical osteoporosis could be diagnosed based on existing data in 104 (67%) at the time of PPFx. Periprosthetic fractures are generally osteoporosis-related. PURPOSE: Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. METHODS: The electronic medical record (EMR) of PPFx patients seen over 4 years in a university orthopedic practice were reviewed. Demographic data and osteoporosis relevant parameters were collected. Prior DXA studies were reviewed, and L1 Hounsfield unit (HU) measurements were performed on CT scans obtained within 2 years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. RESULTS: Records of 156 PPFx patients (115 F/41 M), mean (SD) age 75.4 (11.9), were reviewed. Almost all 153/156 (98%) of these fractures were femoral. Falls caused 139 (89%); 12 (8%) were spontaneous. Mean time post-arthroplasty was 7.9 (6.3) years. Prior fragility fracture(s) occurred in 72 (46%); 14 were PPFx. Osteoporosis was previously diagnosed in 45 (29%) and medications prescribed in 41 (26%). Prior to PPFx, DXA data were available in 62, mean (SD) lowest T-score was - 1.9 (0.9) and was ≤ - 2.5 in 19. CT data were available in 46; mean (SD) L1 HU was 79.0 (29.4) and was ≤ 100 in 35. Based on existing data, clinical osteoporosis could have been diagnosed in 104 (67%) at the time of PPFx. CONCLUSION: Periprosthetic fractures are osteoporosis-related. They occur in older adults, often female, and result from falls; BMD, when assessed, is low. Data available at the time of PPFx often allows osteoporosis diagnosis; this should prompt evaluation and pharmacologic treatment consideration.

Dual-energy X-ray Absorptiometry Trends Among US Medicare Beneficiaries: 2005-2019.

INTRODUCTION: Bone density measured using dual-energy X-ray absorptiometry (DXA) volume, performance site and interpreters have changed in the US since 2005. The purpose of this report is to provide updated trends in DXA counts, rates, place of service and interpreter specialty for the Medicare fee-for-service population. METHODS: The 100 % Medicare Physician/Supplier Procedure Summary Limited Data Set between 2005-2019 was used. DXA counts and annual rates per 10,000 Medicare beneficiaries were calculated. Annual distributions of scan performance location, provider type and interpreter specialty were described. Place of service trends (significance assigned at p < 0.05) of the mean annual share of DXA utilization were identified using linear regression. RESULTS: Annual DXA use per 10,000 beneficiaries peaked in 2008 at 832, declined to 656 in 2015 then increased (p < 0.001) by 38 per year to 807 in 2019. From 2005 to 2019 DXA performance in office settings declined from 70.7 % to 47.2 %. Concurrently, outpatient hospital (OH) DXA increased from 28.6 % to 51.7 %. In 2005, 43.5 % of DXAs were interpreted by radiologists. This increased (p < 0.001) in the office and OH, averaging 0.3 and 2.0 percentage points per year respectively, reaching 73.5 % in 2019. Interpretation by most non-radiologist specialties declined (p < 0.001). CONCLUSIONS: From 2005-2019, total DXA use among Medicare beneficiaries declined reaching a nadir in 2015 then returned to 2005 levels by 2019. Office DXA declined since 2005 with 51.7 % of all scans now occurring in an OH setting. The proportion of DXAs interpreted by radiologists increased over time, reaching 73.5 % in 2019.

Clinical Use of Trabecular Bone Score: The 2023 ISCD Official Positions.

Osteoporosis can currently be diagnosed by applying the WHO classification to bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry (DXA). However, skeletal factors other than BMD contribute to bone strength and fracture risk. Lumbar spine TBS, a grey-level texture measure which is derived from DXA images has been extensively studied, enhances fracture prediction independent of BMD and can be used to adjust fracture probability from FRAX® to improve risk stratification. The purpose of this International Society for Clinical Densitometry task force was to review the existing evidence and develop recommendations to assist clinicians regarding when and how to perform, report and utilize TBS. Our review concluded that TBS is most likely to alter clinical management in patients aged ≥ 40 years who are close to the pharmacologic intervention threshold by FRAX. The TBS value from L1-L4 vertebral levels, without vertebral exclusions, should be used to calculate adjusted FRAX probabilities. L1-L4 vertebral levels can be used in the presence of degenerative changes and lumbar compression fractures. It is recommended not to report TBS if extreme structural or pathological artifacts are present. Monitoring and reporting TBS change is unlikely to be helpful with the current version of the TBS algorithm. The next version of TBS software will include an adjustment based upon directly measured tissue thickness. This is expected to improve performance and address some of the technical factors that affect the current algorithm which may require modifications to these Official Positions as experience is acquired with this new algorithm.

Effect of abdominal tissue thickness on trabecular bone score and fracture risk in adults with diabetes: the Manitoba BMD registry.

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density. However, measures of trabecular microarchitecture from high-resolution peripheral computed tomography are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40 years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference -0.074, P < .001). TBS was lower in women with versus without diabetes (mean difference -0.037, P < .001), and men with versus without diabetes (mean difference -0.007, P = .042). When adjusted for tissue thickness these findings reversed, TBS became greater in men versus women without diabetes (mean difference +0.053, P < .001), in women with versus without diabetes (mean difference +0.008, P < .001), and in men with versus without diabetes (mean difference +0.014, P < .001). During mean 8.7 years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.

Individuals with type 2 diabetes are at increased fracture risk despite having higher bone mineral density (BMD). Previous studies suggest that trabecular bone score (TBS), a measure of bone derived from spine DXA images that can be used to assess fracture risk in addition to BMD, may be lower in individuals with type 2 diabetes. However, TBS is artificially lowered by greater abdominal obesity. We showed that abdominal obesity explained the lower TBS measurements that were seen in individuals with type 2 diabetes. However, even when we considered the effect of abdominal obesity, TBS was still able to predict major fractures in both women and men, with and without diabetes.

Fully automated CT imaging biomarkers for opportunistic prediction of future hip fractures.

OBJECTIVE: Assess automated CT imaging biomarkers in patients who went on to hip fracture, compared with controls. METHODS: In this retrospective case-control study, 6926 total patients underwent initial abdominal CT over a 20-year interval at one institution. A total of 1308 patients (mean age at initial CT, 70.5 ± 12.0 years; 64.4% female) went on to hip fracture (mean time to fracture, 5.2 years); 5618 were controls (mean age 70.3 ± 12.0 years; 61.2% female; mean follow-up interval 7.6 years). Validated fully automated quantitative CT algorithms for trabecular bone attenuation (at L1), skeletal muscle attenuation (at L3), and subcutaneous adipose tissue area (SAT) (at L3) were applied to all scans. Hazard ratios (HRs) comparing highest to lowest risk quartiles and receiver operating characteristic (ROC) curve analysis including area under the curve (AUC) were derived. RESULTS: Hip fracture HRs (95% CI) were 3.18 (2.69-3.76) for low trabecular bone HU, 1.50 (1.28-1.75) for low muscle HU, and 2.18 (1.86-2.56) for low SAT. 10-year ROC AUC values for predicting hip fracture were 0.702, 0.603, and 0.603 for these CT-based biomarkers, respectively. Multivariate combinations of these biomarkers further improved predictive value; the 10-year ROC AUC combining bone/muscle/SAT was 0.733, while combining muscle/SAT was 0.686. CONCLUSION: Opportunistic use of automated CT bone, muscle, and fat measures can identify patients at higher risk for future hip fracture, regardless of the indication for CT imaging. ADVANCES IN KNOWLEDGE: CT data can be leveraged opportunistically for further patient evaluation, with early intervention as needed. These novel AI tools analyse CT data to determine a patient's future hip fracture risk.

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Osteoporosis in men / Osteoporose em homens

Osteoporosis is defined as "a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture". Approximately 40­50 percent of women sustain osteoporotic fractures in their lifetime; as such, it is appropriate that studies initially focused upon females. Despite an increased recognition of osteoporotic fractures in men, there continues to be neglect of this disease in males. This ongoing neglect is inappropriate as 25­33 percent of men in some populations will sustain osteoporotic fractures in their lifetime. Testosterone plays an important role in male skeletal health. However, recent data suggest that estrogen may in fact be the dominant hormone regulating skeletal status in both men and women. BMD measurement may be utilized for osteoporosis diagnosis and to assist with fracture risk prediction in men prior to their sustaining a fracture. Recognizing this need, the International Society for Clinical Densitometry (ISCD) recommended and recently reaffirmed use of a BMD T-score of -2.5 or below be utilized to diagnose osteoporosis in men. Androgen therapy of hypogonadal men may be considered with the caveat that data do not exist to document that this treatment reduces fracture risk. At this time, the data is inadequate to support use of androgen treatment in eugonadal men with osteoporosis. Parathyroid hormone treatment does increase BMD; existing studies have not been of adequate size or duration to document fracture reduction efficacy. Bisphosphonate therapy increases BMD, reduces vertebral fracture risk and is considered the standard of care for osteoporotic men at this point in time.

A osteoporose é definida como "uma doença esquelética sistêmica caracterizada por baixa massa óssea e deterioração da microarquitetura do tecido ósseo com conseqüente aumento da susceptibilidade a fraturas". Aproximadamente 40­50 por cento das mulheres apresentarão uma fratura osteoporótica durante suas vidas, e por isso os estudos iniciais focalizaram o sexo feminino. A despeito do reconhecimento cada vez mais freqüente da ocorrência de fraturas osteoporóticas em homens, a doença continua sendo negligenciada no sexo masculino. Isto não é apropriado na medida em que 25­33 por cento dos homens em algumas populações apresentarão fraturas osteoporóticas durante suas vidas. A testosterona exerce um importante papel na integridade esquelética masculina, contudo dados recentes sugerem que os estrógenos são de fato os hormônios dominantes na regulação esquelética em ambos os sexos. A medida da densidade mineral óssea pode ser utilizada no diagnóstico e para avaliar o risco de fraturas, e a ISCD recomenda que o escore T de -2.5 ou menos seja usado como critério diagnóstico no homem. A terapia androgênica no hipogonadismo masculino deve ser considerada, embora não existam dados sobre redução do risco de fraturas, e no momento não há dados que suportem o uso de andrógenos em homens eugonádicos com osteoporose. O tratamento com paratormônio aumenta a massa óssea, porém os estudos existentes não apresentam amostra e duração suficientes para documentar redução no risco de fraturas. Os bisfosfonatos aumentam a massa óssea, reduzem o risco de fraturas e são considerados como tratamento-padrão para o homem osteoporótico no presente momento.