Ultradistal Radius Research Articles

Pediatric Reference Ranges for Ultradistal Radius Bone Density: Results from the Bone Mineral Density in Childhood Study.

The ultradistal (UD) radius is rich in trabecular bone and is easily measured by dual energy X-ray absorptiometry (DXA). UD radius areal bone mineral density (aBMD) may help identify trabecular bone deficits, but reference data are needed for research and clinical interpretation of this measure. We developed age-, sex-, and population ancestry-specific reference ranges for UD radius aBMD assessed by DXA and calculated Z-scores. We examined tracking of UD radius aBMD Z-scores over 6 years and determined associations between UD radius aBMD Z-scores and other bone measures by DXA and peripheral quantitative computed tomography. Multicenter longitudinal study. A total of 2014 (922 males, 22% African American) children ages 5 to 19 years at enrollment who participated in the Bone Mineral Density in Childhood Study. UD radius aBMD. UD radius aBMD increased nonlinearly with age (P < 0.001) and tended to be greater in males versus females (P = 0.054). Age-, sex-, and ancestry-specific UD radius aBMD reference curves were constructed. UD radius aBMD Z-scores positively associated with Z-scores at other skeletal sites (r = 0.54-0.64, all P < 0.001) and peripheral quantitative computed tomography measures of distal radius total volumetric BMD (r = 0.68, P < 0.001) and trabecular volumetric BMD (r = 0.70, P < 0.001), and was weakly associated with height Z-score (r = 0.09, P = 0.015). UD radius aBMD Z-scores tracked strongly over 6 years, regardless of pubertal stage (r = 0.66-0.69; all P < 0.05). UD radius aBMD Z-scores strongly associated with distal radius trabecular bone density, with marginal confounding by stature. These reference data may provide a valuable resource for bone health assessment in children.

Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH).

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene.Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia.Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (−6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (−4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021).Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients.

Circulating sclerostin is associated with bone mineral density independent of HIV-serostatus

BackgroundLow bone mineral density (BMD) is commonly observed in people living with HIV (PLWH), however the cause for this BMD loss remains unclear. Sclerostin, a bone-derived antagonist to the Wnt/β-catenin-pathway, suppresses bone remodeling and is positively associated with BMD. The goal of the current study was to investigate associations between sclerostin and BMD in a cohort of HIV-seropositive and demographically-matched seronegative women. MethodsThis cross-sectional analysis used a subset of early postmenopausal women enrolled in the Women's Interagency HIV Study (WIHS). BMD was assessed at the lumbar spine, total hip, femoral neck, and distal and ultradistal radius via dual energy x-ray absorptiometry (DXA). Circulating sclerostin was assessed via commercial ELISAs. Univariate and multivariate linear regression modeling tested associations between sclerostin and BMD after adjusting for a variety of BMD-modifying variables. ResultsHIV-seropositive women had significantly reduced BMD at all skeletal sites compared to HIV-seronegative women. There was no difference in sclerostin levels according to HIV-serostatus (0.25 vs 0.27 ng/mL in HIV-seronegative and HIV-seropositive, respectively, p = 0.71). Circulating sclerostin was positively associated with BMD at all sites in both univariate and multivariate models adjusting for HIV status, age, BMI, and race, although the coefficients of association were attenuated in HIV-seropositive women. The positive association between sclerostin and BMD among seropositive women remained statistically significant after adjusting for ART or tenofovir disoproxil fumarate (TDF) use. ConclusionsThe current study suggests that circulating sclerostin is a biomarker for bone mass for both HIV seronegative and seropositive women using and not using ART. The lower coefficients of association between sclerostin and BMD by HIV status may suggest HIV-induced alternation in osteocyte function.

Do patients that fracture with normal DXA-measured BMD have normal bone?

Dual-energy X-ray absorptiometry (DXA) measured bone mineral density (BMD) at the hip and spine is widely used to diagnose osteoporosis. However, patients that sustain "osteoporosis-related" fractures often have normal BMD at these sites. The aim of this study was to explore whether older adults with fracture, but normal reported hip and spine BMD, also have normal bone using additional clinically available assessments. This retrospective electronic medical record study included 387 patients evaluated by a university-based fracture liaison service with spine and hip DXA; 32 (8.3%) had normal spine/hip BMD reported. In this cohort, clinically available bone data including 0.3 and ultradistal radius T-scores, trochanteric T-scores, lumbar spine trabecular bone score (TBS), L1 opportunistic CT Hounsfield units (HU), and femoral cortical index (FCI) were assessed. One or more of the above noted studies were available in 30/32 patients. UD and 0.3 radius results were available in 21 patients, and 18 (85.7%) had T-scores < - 1.0. Trochanteric values were available in 16; T-scores were < - 1.0 in 18.8%. TBS data were available in 24; partially degraded or degraded values were present in 41.7%. L1 opportunistic CT was available in 25 patients, 80% were below normal, and < 150 HU. Finally, femoral cortical index (FCI) was measurable in 9 subjects; 66.7% were below < 0.4. When including all additional available data in the skeletal assessment, only 5/387 (1.3%) were identified with normal bone. Patients with normal spine/hip BMD who sustain fracture rarely have normal bone when all available data are considered.

P44 Homocystinuria is a rare cause of fracture in young patients: a case report

Abstract Background Homocysteinuira is a rare autosomal recessive disorder in the metabolism of sulfur-containing aminoacid caused by mutations in the cystathionine beta-synthase gene which encodes the pyridoxine dependent enzyme cystathionine beta-synthase. It is characterised by significant elevations in plasma and urine homocysteine concentrations and fractures. Methods We describe a case of homocysteinuira in a patient who suffered from a low impact patellar fracture, along with a literature review highlighting the critical relationship between homocysteine level and bone health. Results We reported a 36-year-old female with homocysteinuira due to pyridoxine (B6) unresponsive severe Cystathionine Beta-Synthase deficiency. She developed a right patellar low-impact fracture with osteopenia on X-ray. Examination revealed severe scoliosis with bilateral aphakia (absence of the lens of the eye). Her labs showed, persistent high homocysteine above 100 umol/L (4-10), methionine 383 umol/L (10-42), vitamin D 12 ng/ml. Her spine X-ray revealed severe scoliosis with osteopenia but no fracture. Her DXA scan showed her Z-Score was within the expected range for her age in hip, spine and 1/3 radius areas, however her ultra-distal radius Z-Score was -4.0. Her homocysteine level was mostly higher than 100 due to non-compliance with dietary advice and treatment. The severity of complications primarily depends on the age at diagnosis and the residual cystathionine beta-synthase activity. Most homocysteinuira patients diagnosed in adulthood have severe osteoporosis. Notably, a thinning and lengthening of the long bones result in tall and thin individuals with an appearance like that of Marfan’s syndrome. However, osteoporosis, particularly of the spine, which is associated with scoliosis, is one of the distinguishing features of the disease. High homocysteine levels in homocysteinuric patients impair the function of bone cells that regulate bone remodeling as well as bone material properties such as collagen cross-linking. This imbalance between bone formation and resorption may lead to a low BMD and fracture in patients with. Interestingly, even in general population hyperhomocysteinemia with a plasma level of more than &amp;gt; 13 nmol/ml has been found to be associated with low BMD and an increased risk of fractures that is independent of BMD. Deficiencies in vitamin B6, B12, or folate can lead to increased serum levels of homocysteine as these vitamins act as co-factors for various enzymes involved in homocysteine metabolism. This can be easily rectified with dietary intervention. Conclusion In young patients with a fracture or low BMD, hyperhomocysteinemia could play an important role in the pathogenesis. Homocysteine level should be included in the work up for secondary osteoporosis at young age-group. Simple dietary measures and vitamin B6, folate and B12 supplement should be considered as adjuvant therapeutic option for lowm BMD patients if deficient. Possibly the BMD of the ultra-distal radius is the most sensitive to detect bone changes in hyperhomocysteinemic patients. Disclosures A. Al-Allaf None. T. Paul None. B. Awadh None.

Changes in Skeletal Microstructure Through Four Continuous Years of rhPTH(1-84) Therapy in Hypoparathyroidism.

Bone remodeling is reduced in hypoparathyroidism, resulting in increased areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and abnormal skeletal indices by transiliac bone biopsy. We have now studied skeletal microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT) through 4 years of treatment with recombinant human PTH(1-84) (rhPTH[1-84]) in 33 patients with hypoparathyroidism (19 with postsurgical disease, 14 idiopathic). We calculated Z-scores for our cohort compared with previously published normative values. We report results at baseline and 1, 2, and 4 years of continuous therapy with rhPTH(1-84). The majority of patients (62%) took rhPTH(1-84) 100 μg every other day for the majority of the 4 years. At 48 months, areal bone density increased at the lumbar spine (+4.9% ± 0.9%) and femoral neck (+2.4% ± 0.9%), with declines at the total hip (-2.3% ± 0.8%) and ultradistal radius (-2.1% ± 0.7%) (p < .05 for all). By HR-pQCT, at the radius site, very similar to the ultradistal DXA site, total volumetric BMD declined from baseline but remained above normative values at 48 months (Z-score + 0.56). Cortical volumetric BMD was lower than normative controls at baseline at the radius and tibia (Z-scores -1.28 and - 1.69, respectively) and further declined at 48 months (-2.13 and - 2.56, respectively). Cortical porosity was higher than normative controls at baseline at the tibia (Z-score + 0.72) and increased through 48 months of therapy at both sites (Z-scores +1.80 and + 1.40, respectively). Failure load declined from baseline at both the radius and tibia, although remained higher than normative controls at 48 months (Z-scores +1.71 and + 1.17, respectively). This is the first report of noninvasive high-resolution imaging in a cohort of hypoparathyroid patients treated with any PTH therapy for this length of time. The results give insights into the effects of long-term rhPTH(1-84) in hypoparathyroidism. © 2020 American Society for Bone and Mineral Research.

Bone Adaptation in Adult Women Is Related to Loading Dose: A 12-Month Randomized Controlled Trial.

ABSTRACTAlthough strong evidence exists that certain activities can increase bone density and structure in people, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical trial design. The degree to which strain rate and magnitude govern bone adaptation in humans has never been prospectively tested. Here, we studied the effects of a voluntary upper extremity compressive loading task in healthy adult women during a 12‐month prospective period. A total of 102 women age 21 to 40 years participated in one of two experiments: (i) low (n = 21) and high (n = 24) strain magnitude; or (ii) low (n = 21) and high (n = 20) strain rate. Control (n = 16) no intervention. Strains were assigned using subject‐specific finite element models. Load cycles were recorded digitally. The primary outcome was change in ultradistal radius integral bone mineral content (iBMC), assessed with QCT. Interim time points and secondary outcomes were assessed with high resolution pQCT (HRpQCT) at the distal radius. Sixty‐six participants completed the intervention, and interim data were analyzed for 77 participants. Likely related to improved compliance and higher received loading dose, both the low‐strain rate and high‐strain rate groups had significant 12‐month increases to ultradistal iBMC (change in control: −1.3 ± 2.7%, low strain rate: 2.7 ± 2.1%, high strain rate: 3.4 ± 2.2%), total iBMC, and other measures. “Loading dose” was positively related to 12‐month change in ultradistal iBMC, and interim changes to total BMD, cortical thickness, and inner trabecular BMD. Participants who gained the most bone completed, on average, 128 loading bouts of (mean strain) 575 με at 1878 με/s. We conclude that signals related to strain magnitude, rate, and number of loading bouts contribute to bone adaptation in healthy adult women, but only explain a small amount of variance in bone changes. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Bone microstructure and volumetric bone mineral density in patients with hyperuricemia with and without psoriasis.

Hyperuricemia (HU) and gout are co-conditions of psoriasis and psoriatic arthritis. Current data suggest a positive association between HU and areal bone mineral density (BMD) and a negative influence of psoriasis on local bone, even in the absence of arthritis. However, the influence of the combination of HU and psoriasis on bone is still unclear. The aim of this study was to assess the impact of HU with and without psoriasis on bone microstructure and volumetric BMD (vBMD). Healthy individuals with uric acid levels within the normal range (NU), with hyperuricemia (HU), patients with hyperuricemia and psoriasis (PSO + HU), and patients with uric acid within the normal range and psoriasis (PSO + NU) were included in our study. Psoriasis patients had no current or past symptoms of arthritis. Average, trabecular, and cortical vBMD (mgHA/cm3); trabecular number (Tb.N, 1/mm) and thickness (Tb.Th, mm); inhomogeneity of the network (1/N.SD, mm); and cortical thickness (Ct.Th., mm) were carried out at the ultradistal radius using high-resolution peripheral quantitative computed tomography. In addition, bone turnover markers such as DKK-1, sclerostin, and P1NP were analyzed. In total, 130 individuals were included (44 NU participants (34% female), 50 HU (24%), 16 PSO + HU (6%), 20 PSO + NU (60%)). Subjects were aged: NU 54.5 (42.8, 62.1), HU 57.5 (18.6, 65.1), PSO + HU 52.0 (42.3, 57.8), and PSO + NU 42.5 (34.8, 56.8), respectively. After adjusting for age, sex, BMI, and diabetes, patients in the HU group revealed significantly higher values of cortical vBMD (p < 0.001) as well as cortical thickness (p = 0.04) compared to the NU group. PSO + NU showed no differences to NU, but PSO + HU demonstrated both lower average (p = 0.03) and trabecular vBMD (p = 0.02). P1NP was associated with average, cortical, and trabecular vBMD as well as cortical thickness while sclerostin levels were related to trabecular vBMD. Hyperuricemia in otherwise healthy subjects was associated with a better cortical vBMD and higher cortical thickness. However, patients with both psoriasis and hyperuricemia revealed a lower vBMD.

Homocystinuria a rare cause of low BMD in young patients: A case report with literature review

Background: Homocystinuira is a rare autosomal recessive disorder in the metabolism of sulfur-containing amino acid caused by mutations in the cystathionine beta-synthase gene which encodes the pyridoxine (Vitamin B6) dependent enzyme cystathionine beta-synthase. It is characterized by significant elevations in plasma and urine homocysteine concentrations, which could be associated with increased risk of fracture. Methods: We describe a case of Homocystinuria who suffered from a low impact patellar fracture with a literature review to highlight the critical relationship between homocysteine level and bone health. Results: We reported a 36-year-old female with a diagnosis of Homocystinuria due to pyridoxine (B6) unresponsive severe Cystathionine Beta-Synthase deficiency. After a minor knee injury she developed a right patellar fracture and her X-ray revealed osteopenia. On examination, she has severe scoliosis in the spine with bilateral aphakia (absence of the lens of the eye). Her labs showed, persistent high Homocysteine above 100 umol/L, Methionine: 383 umol/L (10-42), Vitamin D 12 ng/ml. Her spine X-ray revealed very severe scoliosis with osteopenia but no vertebra fracture. Her DXA scan showed her Z-Score was within the expected range for her age in hip, spine and 1/3 radius areas, however her ultra-distal radius Z-Score was -4.0. Her Homocystine level was mostly higher than 100 due to non-compliance with dietary advice and treatment. High homocysteine levels in Homocystinuric patients impair the function of bone cells that regulate bone remodeling as well as bone material properties such as collagen cross-linking. This imbalance between bone formation and resorption may lead to a low BMD and fracture in patients with homocystinuria. Interestingly, even in general population hyperhomocystinemia with a plasma level of more than > 13 nmol/ml has been found to be associated with low BMD and an increased risk of fractures that is independent of BMD. Deficiencies in vitamin B6, B12, or folate can lead to increased serum levels of Homocysteine as these vitamins act as co-factors for various enzymes involved in homocysteine metabolism. This can be easily rectified with dietary intervention. Conclusion: In young patients with a fracture or low bone mineral density, hyperhomocystinemia could play an important role in the pathogenesis. This should be included in the work up for secondary causes for osteoporosis for this age-group. Simple dietary measures and vitamin B6, folate and B12 supplement should be considered as adjuvant therapeutic option for any patient with osteoporosis and fractures, if deficient. Possibly the BMD of the ultra-distal radius is the most sensitive to detect bone changes in these patients.

Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.

In adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection. Forty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6kg/m2; median age 57, range 50-69years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors. In regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2=0.23; β=0.03; p=0.044) and higher radius cortical BMD (R2=0.43; β=8.4; p=0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2=0.38; β=0.96; p=0.050), higher radius trabecular number (R2=0.31; β=0.01; p=0.026), lower tibia and radius trabecular separation (tibia: R2=0.30; β=-0.003; p=0.038; radius: R2=0.35; β=-0.003; p=0.021), and higher radius bone stiffness (R2=0.45; β=0.38; p=0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2=0.44; β=4.06; p=0.036), higher tibia bone stiffness (R2=0.46; β=3.06; p=0.050), and higher tibia estimated failure load (R2=0.46; β=0.17; p=0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2=0.39; β=-41.2; p=0.042), lower radius trabecular number (R2=0.34; β=-0.44; p=0.009) and greater radius trabecular separation (R2=0.42; β=0.16; p=0.002), while TDF use without a PI was not associated with reduced bone quality. In adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.

Impact of reference point selection on DXA-based measurement of forearm bone mineral density.

Forearm fractures are clinically important outcomes from the perspective of morbidity, health care costs, and interruption of work. BMD of the forearm, as derived by dual-energy x-ray absorptiometry (DXA), is a better predictor of fracture at the forearm compared with BMD measured at other sites. However, very few studies have evaluated the technical aspects of selecting the ROI for forearm BMD measurement. This study aimed to compare the BMD values measured at the 1/3 radius site using three different reference points: the ulnar styloid process, the radial endplate, and the bifurcation of the ulna and radius. Healthy Chinese patients participating in the control group of an ongoing study at Zhejiang Provincial People's Hospital were recruited for this study. For each patient, a DXA scan (GE Lunar Prodigy) of the forearm was performed and BMD values were separately calculated using each of the three reference points to identify the ROI. Pearson correlation coefficients were calculated to examine the correlation between the BMD measures derived from each reference point. The F test and independent t test were applied for more robust analysis of the differences in the variances and means. Sixty-eight healthy Chinese volunteers agreed to participate in this study. The root mean square standard deviation (RMS-SD) percentages of BMD values measured at the 1/3 radius site were 2.19%, 2.23%, and 2.20% when using the ulnar styloid process, radial endplate, and the bifurcation of the ulna and radius as the reference points, respectively. Pearson's correlation coefficients for all pairwise comparisons among these three groups were greater than 0.99. F tests and independent t tests showed p values ranging from 0.92 to 0.99. However, we observed that among 10% of patients, choosing an ROI at the ulnar styloid process led to an inability to accurately determine the BMD at the ultra-distal radius. Given equal ability to determine BMD at the 1/3 radius accurately, the radial endplate or the bifurcation of the ulna and radius should be preferentially selected as the reference point for routine forearm BMD measurements in order to avoid situations in which the ultra-distal radius BMD cannot be determined.

Characteristics of ultradistal radius bone density during childhood: results from the Bone Mineral Density in Childhood Study

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Long-term denosumab treatment restores cortical bone loss and reduces fracture risk at the forearm and humerus: analyses from the FREEDOM Extension cross-over group

SummaryUpper limb fractures (including wrist, forearm, and humerus) represent a significant burden among postmenopausal women with osteoporosis. Up to 7 years of treatment with denosumab resulted in an increase in bone mineral density and decrease in fractures in upper limb sites.IntroductionUpper limb (wrist, forearm, and humerus) fractures are a significant burden in osteoporosis, associated with significant morbidity and mortality. Denosumab, a monoclonal antibody against RANK ligand, increases bone mineral density (BMD) and decreases vertebral, nonvertebral, and hip fractures. Here, we evaluated the long-term effect of denosumab treatment on upper limb fracture risk and BMD.MethodsIn the FREEDOM trial, subjects were randomized 1:1 to receive every-6-month denosumab 60 mg or placebo subcutaneously for 3 years, after which all subjects could receive denosumab for up to 7 years (Extension). Among placebo subjects who completed FREEDOM and enrolled in the Extension, wrist, forearm, humerus, and upper limb fracture rates and rate ratios between different time periods (FREEDOM years 1–3, Extension years 1–3, and Extension years 4–7) were computed. BMD at the ultradistal radius, 1/3 radius, and total radius was analyzed in a subset of subjects in a BMD substudy.ResultsThis analysis included 2207 subjects (116 in the BMD substudy). Fracture rates decreased over the 7-year Extension; fracture rate ratios between Extension years 4–7 (denosumab) and FREEDOM years 1–3 (placebo) reduced significantly for the wrist (0.57), forearm (0.57), humerus (0.42), and upper limb (0.52; p < 0.05 for all). Percentage increase in BMD from Extension baseline at the ultradistal radius, 1/3 radius, and total radius was significant by Extension year 7 (p < 0.05 for all).ConclusionsLong-term treatment with denosumab decreases upper limb fracture risk and increases forearm BMD, suggesting beneficial effects on both cortical and trabecular bone accruing over time.

A multi-imaging modality study of bone density, bone structure and the muscle - bone unit in end-stage renal disease.

End stage renal disease (ESRD) is associated with sarcopenia and skeletal fragility. The objectives of this cross-sectional study were to (1) characterize body composition, bone mineral density (BMD) and bone structure in hemodialysis patients compared with controls, (2) assess whether DXA areal BMD (aBMD) correlates with peripheral quantitative CT (pQCT) measures of volumetric BMD (vBMD), cortical dimensions and MRI measures of trabecular microarchitecture, and (3) determine the magnitude of bone deficits in ESRD after adjustment for muscle mass. Thirty ESRD participants, ages 25 to 64 years, were compared with 403 controls for DXA and pQCT outcomes and 104 controls for MRI outcomes; results were expressed as race- and sex- specific Z-scores relative to age. DXA appendicular lean mass index (ALMI kg/m2) and total hip, femoral neck, ultradistal and 1/3rd radius aBMD were significantly lower in ESRD, vs. controls (all p < 0.01). pQCT trabecular vBMD (p < 0.01), cortical vBMD (p < 0.001) and cortical thickness (due to a greater endosteal circumference, p < 0.02) and MRI measures of trabecular number, trabecular thickness, and whole bone stiffness were lower (all p < 0.01) in ESRD, vs. controls. ALMI was positively associated with total hip, femoral neck, ultradistal radius and 1/3rd radius aBMD and with tibia cortical thickness (R = 0.46 to 0.64). Adjustment for ALMI significantly attenuated bone deficits at these sites: e.g. mean femoral neck aBMD was 0.79 SD lower in ESRD, compared with controls and this was attenuated to 0.33 with adjustment for ALMI. In multivariate models within the dialysis participants, pQCT trabecular vBMD and cortical area Z-scores were significant and independently (all p < 0.02) associated with DXA femoral neck, total hip, and ultradistal radius aBMD Z-scores. Cortical vBMD (p = 0.01) and cortical area (p < 0.001) Z-scores were significantly and independently associated with 1/3rd radius areal aBMD Z-scores (R2 = 0.62). These data demonstrate that DXA aBMD captures deficits in trabecular and cortical vBMD and cortical area. The strong associations with ALMI, as an index of skeletal muscle, highlight the importance of considering the role of sarcopenia in skeletal fragility in patients with ESRD.

Quantitative Computed Tomography (QCT) of the Distal Forearm in Men Using a Spiral Whole-Body CT Scanner – Description of a Method and Reliability Assessment of the QCT Pro Software

The Mr F study investigates the pathogenesis of low trauma distal forearm fractures in men and includes volumetric bone mineral density (vBMD) measurements at the ultradistal forearm as there are no current data. A standard 64 slice CT scanner was used to determine if it was possible to adapt the existing Mindways quantitative computed tomography Pro software for measuring vBMD values at the hip and spine sites. For calculation of intra- and interobserver reliability 40 forearm scans out of the 300 available were chosen randomly. The images were analyzed using the Slice Pick module and Bone Investigational Toolkit. The 4% length of the radius was chosen by measuring the length of the radius from the scaphoid fossa distally to the radial head. The acquired image then underwent extraction, isolation, rotation, and selection of region of interest in order to generate a report on vBMD. A cross-sectional image was created to allow the generation of data on the cortical and trabecular components separately. Repeat analyses were undertaken by 3 independent observers who were blinded as to whether the image was from a participant with or without fracture. The images were presented in random order at each time point. The following parameters were recorded: cortical cross sectional area, total vBMD, trabecular vBMD, and cortical vBMD (CvBMD). Data were analyzed by calculating intraclass correlation coefficients for intra- and interobserver reliability. The lowest values occurred at the CvBMD with intraobserver reliability of 0.92 (95% confidence interval [CI] of 0.86–0.96) and interobserver reliability of 0.92 (95% CI 0.89–0.96). All other parameters had reliability values between 0.97 and 0.99 with tighter 95% CI than for CvBMD. The method of adapting the Mindways Pro software using a standard CT to produce vBMD and structural data at the ultradistal radius is reliable.

Is radius bone mineral density helpful for fracture risk assessment?

AbstractAlthough peripheral DXA is not recommended for the diagnosis of osteoporosis or to monitor osteoporotic treatments, its use for fracture risk assessment is supported by several studies. In addition, its potential interest is supported by the recent demonstration, in prospective cohorts, of the contribution of distal radius microstructure and strength, assessed by high-resolution peripheral QCT (HRpQCT), to predict incident fractures beyond the classical clinical tools (femoral neck BMD and FRAX). Indeed, areal BMD measured by DXA at the ultra-distal radius is highly correlated with bone strength derived from HRpQCT measurements at the same site. Ultra-distal radius areal BMD is therefore highly associated with fracture risk, with associations of higher magnitude than at the “classically recommended” one-third distal radius. Furthermore, ultra-distal radius areal BMD is also associated with incident fractures in non-osteoporotic women in women with T-score &gt; –2.5 SD on hip and spine DXA or women with FRAX score below the intervention threshold for age. Since more than half of low-trauma fractures occur in individuals not identified as being at high risk by BMD testing at the spine or hip, radius bone mineral density may help to refine fracture risk in patients with osteopenia defined by central DXA (spine or hip), or relatively few clinical risk factors.

Recovery of Bone Mineral Mass After Upper Limb Fractures in Children and Teenagers.

Loss of bone mineral mass and muscle atrophy are predictable consequences of cast-mediated immobilization following wrist and forearm fractures. This study aimed to prospectively determine whether previously reported lower bone mineral mass following immobilization for wrist and forearm fractures in children and teenagers had recovered at 6- and 18-month follow-up. We recruited 50 children and teenagers who underwent a cast-mediated immobilization for a forearm or wrist fracture. Dual-energy x-ray absorptiometry scans of different skeletal sites were performed at the time of fracture, at cast removal, at 6 and at 18-month follow-up. Injured patients were paired with healthy controls according to sex and age. Dual-energy x-ray absorptiometry values were compared between groups and the injured and uninjured forearms of the patients. At the time of fracture, injured and healthy subjects showed no differences between their bone mineral density (BMD) and bone mineral content (BMC) z-scores at the lumbar spine, or between their BMDs at the peripheral wrist. At cast removal, upper limb bone mineral variables were significantly lower in the injured group (except for the ultradistal radius) than in the uninjured group, with differences ranging from 3.8% to 10.2%. No residual decrease in bone mineral variables was observed at any upper limb site at 6- and 18-month follow-up (28 injured patients). Significant residual increases in the BMDs and BMCs were observed for the injured group's ultradistal radius and whole wrists (+4.8% to +5.2%). A rapid bone mass reversal occurs by resumption of mobilization, with full bone recovery 6 months after a forearm or wrist fracture. Finally, healing bone callus could introduce a bias into the interpretation of BMD and BMC data at the fracture site, not only at cast removal but also 18 months after the fracture.

Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis

PurposeWrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture.MethodsForearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463).ResultsAfter 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (−0.42; 95% CI −1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (−1.66%; 95% CI −2.27, −1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11).ConclusionsCompared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol.

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median -2.2% [interquartile range (IQR) -5.9-1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR -3.2-7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.

Correlation of lumbar spine TBS with distal radius and tibial trabecular density and structure measured with HR-pQCT in men and women in the Toronto Cohort of the Canadian Multicentre Osteoporosis Study (CaMOS)

Introduction To better estimate the risk of bone fractures, both bone mineral density (BMD) and microarchitecture should be measured. Dual-energy X-ray absorptiometry(DXA) scans are clinically used to provide information about BMD and can be used to determine trabecular bone score (TBS), which gives an estimate of trabecular microarchitecture for lumbar spine(L1-L4). High-resolution pQCT (HRpQCT) is an in vivo measurement of bone microstructure of the distal radius and tibia and its images can be converted to finite elements for estimation of bone strength. Objectives This study assessed whether aBMD and TBS measured at central sites correlates with trabecular microstructure measured by HRpQCT at peripheral sites in men and women. Methods This cross-sectional analysis included participants from the Toronto cohort of CaMOS. HRpQCT and lumbar spine TBS were performed. Bone microstructure was determined from HRpQCT images and lumbar spine TBS from DXA scans. Correlations between HRpQCT and DXA measured indices in men and women were calculated. Results 197 participants were included (70M, 127F) with a mean age of 70 years. HRpQCT variables were significantly different among men and women with the exception of cortical vBMD (p=0.08) at distal radius. Correlations between aBMD at different skeletal sites and HRpQCT indices varied widely. The strongest correlation was seen at the ultra-distal radius (r 0.5-0.8, p Conclusion There is a clear difference in bone quality based on sex and age according to our assessment of bone microarchitecture and strength parameters. The weak association between lumbar spine TBS and peripheral HRpQCT indices may suggest that bone microstructure varies with site. Using them in combination may give a better understanding of overall fracture risk of an individual. Fig .