Areal Bone Mineral Density Research Articles

FRI038 Differences In Bone Accrual Over One Year In Young Girls With Obesity Compared To Normal Weight Controls

Abstract Disclosure: S. Kaur: None. V. Singhal: None. L.A. Haidar: None. M. Bredella: None. M. Misra: None. Introduction: Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We aimed to assess changes in areal and volumetric BMD, bone geometry and microarchitecture, and estimates of bone strength over one year in young females with moderate to severe obesity compared to their normal-weight counterparts. Methods: We recruited females between 13-25 years of age with moderate to severe obesity (OB) (n=21) and compared their bone accrual over one year with normal-weight controls (NWC) (n=50). Dual-energy X-ray absorptiometry to assess areal BMD (aBMD), high-resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture, and micro finite element analysis for estimates of bone strength was used. Analyses were controlled for age and race. Results: The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity at baseline. OB had higher weight and BMI (p<0.0001 for both) and younger menarchal age (p=0.022) than NWC. Over one year, there was no difference between the groups for change in height, weight, and BMI. However, OB did not demonstrate the increase in total hip BMD observed in NWC (p=0.03) over a year. OB also had lesser increases in percent cortical area, cortical thickness, cortical and total vBMD at the radius over a year than the NWC group (p≤0.037 for all). The groups did not differ for tibial bone accrual. Conclusions: Our study demonstrates that longitudinal bone accrual over one year is impaired at the total hip and radius in adolescents and young adult females with obesity compared to normal-weight controls, while no differences are observed in tibial bone accrual. This raises concerns regarding future bone health in women with obesity, particularly at certain skeletal sites. Presentation: Friday, June 16, 2023

OR13-03 Assessment Of Skeletal Health Including Bone Density, Turnover, Microarchitecture And Osteoporosis In Patients With Sheehan’s Syndrome: A Prospective, Multicentric Study In Asian Indians

Abstract Disclosure: L. Das: None. B. Laway: None. J. Sahoo: None. S.K. Bhadada: None. P. Dutta: None. Introduction: Sheehan’s syndrome (SS) is a rare cause of hypopituitarism. Evidence on skeletal health in patients with this condition is limited, and data on bone geometry, structure and volumetric bone mineral density (BMD) are lacking. We aimed to comprehensively explore skeletal fragility in a multicentric cohort of treated SS. Patients and Methods: Patients with SS were recruited for analysis of demographic, clinico-biochemical and hormonal profile including bone turnover markers. Areal BMD, T- and Z-scores and trabecular bone score (TBS) were evaluated using DXA. In a subset of patients (n=29) as well as age-and BMI-matched controls (n=34), high-resolution peripheral quantitative computed tomography (HRpQCT, XtremeCT II, Scanco Medical AG, Switzerland) was performed to assess bone geometry and microarchitecture. Results: There were a total of 105 patients with SS with a mean age 45.2 ± 10.5 years and a lag of 7.4 ± 5.5 years from disease onset to diagnosis. Regular levothyroxine replacement was ongoing in 91.2% and glucocorticoid replacement in 86.1% of the cohort. Past HRT replacement was done in 66.7% patients. Bone turnover markers (P1NP, CTX) were not significantly different between cases and controls. The T- score [-2.3 (-3.0 to -1.6) vs -1.5 (-3.0 to -0.7)] and Z-score [-1.4 (-2.1 to -1.2) vs -0.6 (-2.1 to -0.1)] at the lumbar spine (LS) and the T- score [-1.8 (-2.3 to -1.3) vs -0.8 (-2.1 to -0.1)] and Z-score [-1.1 (-1.7 to -0.4) vs -0.4 (-1.0 to 0.2)] at the femoral neck (FN) were lower in cases as compared to controls (trend towards significance). Osteopenia or osteoporosis was prevalent in significantly greater proportion of the cases as compared to controls, at LS (96.3% vs 64.7%), FN (91.7% vs 47%) and ultradistal radius (65.2% vs 11.8%). Bone microarchitectural assessment showed no significant differences between TBS, or bone geometry. However, trabecular volumetric bone mineral density was higher at both tibia (p<0.05) and radius (p>0.05) in cases as opposed to age-and BMI-matched controls. There was a weak negative correlation between glucocorticoid and levothyroxine replacement duration and BMD at both LS and FN (p<0.05), but not with replacement dose. Conclusion: Osteopenia-osteoporosis is highly prevalent in SS. BMD at both LS and FN is negatively correlated with duration of glucocorticoid and levothyroxine exposure. There are no significant differences in bone microarchitecture or geometry but tibial trabecular volumetric BMD is greater in treated SS. Presentation: Friday, June 16, 2023

THU419 Comprehensive Evaluation Of Osteoporosis And Impaired Bone Micro Architecture In Patients With Transfusion Dependent Beta Thalassemia

Abstract Disclosure: P. Dutta: None. comprehensive evaluation of osteoporosis and impaired bone micro architecture in patients with transfusion dependent beta thalassemia Authors: Pinaki Dutta, Liza Das, Alka Khadwal, Pankaj Malhotra, Sanjay Kumar Bhadada, Vandana Dhiman, Vivek Sharma, Raman Introduction: Thalassemia-related bone disease is an entity that includes low bone mass, fractures and impaired bone microarchitecture. The current study was designed to evaluate the prevalence and determinants of low bone mass, osteoporosis and microarchitectural parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with transfusion-dependent thalassemia (TDT). Patients and Methods TDT patients (n=42) and age- and BMI-matched controls (n=40) were recruited. Demographic, biochemical and hormonal parameters were assessed. Bone mineral density (BMD), T- and Z- scores were measured by DEXA using the HOLOGIC Discovery A Viewer 6 machine. Bone microarchitecture was estimated by HR-pQCT (XtremeCT II, Scanco Medical AG, Switzerland). Results: The mean age of thalassemia patients at recruitment was 26.9 ± 6.5 years and that of controls was 28.9 ± 7.9 years. The mean age of transfusion initiation was 7 months (IQR 3-18) and the median number of transfusions required was 24 (15-25) annually. Serum calcium in cases (8.87 ± 0.67mg/dl) was significantly lower than the controls (9.40 ± 0.45mg/dl), with 9 patients having hypocalcemia and 7 of these having hypoparathyroidism. Hypogonadism was present in 40.4% patients. Bone turnover markers (P1NP, β-CTX) were not significantly different between cases and controls, except alkaline phosphatase (ALP) which was higher in the cases (102.6 ± 60.7 U/l) as opposed to controls (78.2 ± 32.1 U/l). There was a significant correlation between ALP and liver dysfunction (alanine transaminase exceeding the upper normal limit) (r = 0.36, p=0.01) and 63.6% of those with elevated ALP had liver dysfunction. Low bone mass (Z ≤−2) was present in significantly greater proportion of patients versus controls at femoral neck (29.3% vs 2.4%) and at lumbar spine (52.4% vs 14.7%). Total, cortical and trabecular volumetric bone mineral density were significantly lower in cases as compared to controls(p<0.05). The trabecular number was significantly lower (p<0.0001) and trabecular separation significantly higher at radius and tibia (p<0.001). Cortical thickness at radius and tibia were also significantly lower in cases than controls (p<0.0001). Conclusion: Patients with transfusion-dependent thalassemia have significantly lower areal and volumetric BMD (both cortical and trabecular). The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness at both radius and tibia. Presentation: Thursday, June 15, 2023

OR13-04 Risk Of Wrist Fracture In Gastric Bypass Compared To Gastric Banding As Estimated By The Load-To-Strength Ratio

Abstract Disclosure: G.H. Jung: None. B. Zahedi: None. K. Lindeman: None. C.C. Rushin: None. M.C. Cheney: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Background: Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) lead to long-term deficits in bone density but are also accompanied by decreased weight, which may lower the impact force with falls. Given that risk of fracture is dependent on both bone strength and the external force applied to bone, the clinical implications of these opposing effects are unclear. The aim of this study is to compare the long-term skeletal impact of RYGB and AGB using a biomechanical evaluation of load-to-strength ratio as a surrogate for fracture risk. Methods: We examined a cohort of adults who received RYGB and AGB surgery ≥ 10 years ago (RYGB: n=25; AGB: n=25). We computed the load-to-strength ratio at the distal radius as a ratio of impact force to bone strength, with higher load-to-strength ratios representing a higher susceptibility to fracture. Impact force (F) was calculated for a forward fall via a single-spring biomechanical model. High-resolution peripheral quantitative CT was used to estimate bone strength via microfinite element analysis. Participants also had dual-energy X-ray absorptiometry measurements of areal bone mineral density (aBMD) at the spine, hip, and distal radius, along with laboratory evaluations (parathyroid hormone, PTH; C-telopeptide, CTX; type 1 procollagen, P1NP; 25OH-vitamin D). Differences in bone outcomes between RYGB and AGB groups were compared using generalized linear modeling in R version 4.2.2 and adjusted for age, sex/menopausal status, and race/ethnicity. Results: The RYGB and AGB groups were each comprised of 22 women and 3 men. Compared to AGB, the RYGB group was younger (56 vs 62 years), had more premenopausal women (41% vs 9%), more individuals who identified as Black (36% vs 8%) and longer duration since surgery (13 vs 11 years) (p<0.05 for all). Current BMI (34.5 kg/m^2) was similar between groups, although postsurgical weight loss was higher in RYGB (45 vs. 27 kg, p<0.001). In multivariate analysis, in comparison to AGB, the RYGB group had 98% higher CTX and 34% higher P1NP levels (P<0.01 for both), as well as 20% lower total vBMD at the distal radius, 12% lower total hip, 10% lower femoral neck and 8% lower spinal aBMD (P<0.05 for all). Although impact forces were similar in the 2 groups, RYGB had a 12% lower estimated bone strength (3768 ± 182 vs. 4236 ± 193 N, p=0.01). Load-to-strength ratio was numerically higher in RYGB as compared with AGB (0.78 ± 0.05 vs 0.69± 0.06, p=0.1), suggestive of higher fracture risk, although this did not reach statistical significance. Conclusions: Despite achieving similar postoperative weight as AGB, RYGB patients had lower estimated bone strength at the distal radius, higher bone turnover markers, lower BMD and a trend for higher load-to-strength ratio ≥10 years after surgery. Taken together, these results indicate the long-term deleterious skeletal effects are more concerning with RYGB than AGB. Presentation: Friday, June 16, 2023

CT and MR for bone mineral density and trabecular bone score assessment in osteoporosis evaluation

Dual energy X-ray absorptiometry (DXA) is widely used modality for measuring bone mineral density (BMD). DXA is used to measure the quantitative areal BMD of bone, but has the disadvantage of not reflecting the bone architecture. To compensate for this disadvantage, trabecular bone score (TBS), a qualitative parameter of trabecular microarchitecture, is used. Meanwhile, there have been recent attempts to diagnose osteoporosis using the Hounsfield unit (HU) from CT and MR-based proton density fat fraction (PDFF) measurements. In our study, we aimed to find out the correlation between HU/PDFF and BMD/TBS, and whether osteoporosis can be diagnosed through HU/PDFF. Our study revealed that the HU value showed a moderate to good positive correlation with BMD and TBS. PDFF showed a fair negative correlation with BMD and TBS. In diagnosing osteopenia and osteoporosis, the HU value showed good performance, whereas the PDFF showed fair performance. In conclusion, both HU values and PDFF can play a role in predicting BMD and TBS. Both HU values and PDFF can be used to predict osteoporosis; further, CT is expected to show better results.

Photon-Counting CT Material Decomposition in Bone Imaging.

The accurate screening of osteoporosis is important for identifying persons at risk. The diagnosis of bone conditions using dual X-ray absorptiometry is limited to extracting areal bone mineral density (BMD) and fails to provide any structural information. Computed tomography (CT) is excellent for morphological imaging but not ideal for material quantification. Advanced photon-counting detector CT (PCD-CT) possesses high spectral sensitivity and material decomposition capabilities to simultaneously determine qualitative and quantitative information. In this study, we explored the diagnostic utility of PCD-CT to provide high-resolution 3-D imaging of bone microarchitecture and composition for the sensitive diagnosis of bone in untreated and ovariectomized rats. PCD-CT accurately decomposed the calcium content within hydroxyapatite phantoms (r = 0.99). MicroCT analysis of tibial bone revealed significant differences in the morphological parameters between the untreated and ovariectomized samples. However, differences in the structural parameters of the mandible between the treatment groups were not observed. BMD determined with microCT and calcium concentration decomposed using PCD-CT differed significantly between the treatment groups in both the tibia and mandible. Quantitative analysis with PCD-CT is sensitive in determining the distribution of calcium and water components in bone and may have utility in the screening and diagnosis of bone conditions such as osteoporosis.

Cross-Calibration Study of The Stratos And Hologic QDR 4500A Dual-Energy X-Ray Absorptiometers to Assess Bone Mineral Density And Body Composition

The objective of the study was to assess the agreement between the Stratos (DMS) and QDR 4500A (Hologic) DXAs in determining whole body and regional aBMD, as well as whole body composition.Fifty-five individuals (46 women: 84%) with a mean age of 41 ± 13.0 years (range: 20 to 64) and a mean BMI of 31.9 ± 10 kg/m² (range: 12.2 to 49.5) were consecutively scanned on the same day using the two devices. Predictive equations for areal bone mineral density (aBMD) and whole body composition (WBC) were derived from linear regression of the data.The two DXAs were highly correlated (p<0.001 for all parameters) with a correlation coefficient (r) ranging from 0.89 to 0.99 for aBMD (r=0.89 for whole body, r=0.92 for radius, r=0.95 for femoral neck, r=0.96 for total hip, and r=0.99 for L1-L4). For WBC, the r value was 0.98 for lean tissue mass (LTM) and 1.0 for fat mass (FM). Paired t-tests indicated a statistically significant bias between the two DXAs for the majority of measurements, requiring the determination of specific cross-calibration equations. Compared to QDR 4500A, Stratos underestimated whole body aBMD and LTM and overestimated neck and hip aBMD and whole body FM. Conversely, no significant bias was demonstrated for mean aBMD at L1-L4 and radius. For whole body aBMD and FM, the concordance between the two DXAs was influenced by BMI.Despite a high concordance between the two DXAs, the systematic bias for aBMD and WBC measurements illustrates the need to define cross-calibration equations to compare data across systems.

Osteogenic Effects of KY-054, a Novel Coumarin Derivative on Femur Cortical Bone in Ovariectomized Female Rats.

Osteoporosis is treated with oral and parenteral bone resorption inhibitors such as bisphosphonates, and parenteral osteogenic drugs including parathyroid hormone (PTH) analogues and anti-sclerostin antibodies. In the present study, we synthesized KY-054, a 4,6-substituted coumarin derivative, and found that it potently promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity at 0.01-1 µM in mouse-derived mesenchymal stem cells (ST2 cells) and rat bone marrow-derived mesenchymal stem cells (BMSCs). In the ovariectomized (OVX) rats, KY-054 (10 mg/kg/d, 8 weeks) increased plasma bone-type ALP activity, suggesting in vivo promoting effects on osteoblast differentiation and/or activation. In dual-energy X-ray absorption (DEXA) scanning, KY-054 significantly increased the distal and diaphyseal femurs areal bone mineral density (aBMD) that was decreased by ovariectomy, indicating its beneficial effects on bone mineral contents (BMC) and/or bone volume (BV). In micro-computed tomography (micro-CT) scanning, KY-054 had no effect on metaphysis trabecular bone loss and microarchitecture parameters weakened by ovariectomy, but instead increased metaphysis and diaphysis cortical bone volume (Ct.BV) and cortical BMC (Ct.BMC) without reducing medullary volume (Med.V), resulting in increased bone strength parameters. It is concluded that KY-054 preferentially promotes metaphysis and diaphysis cortical bone osteogenesis with little effect on metaphysis trabecular bone resorption, and is a potential orally active osteogenic anti-osteoporosis drug candidate.

A Pilot Study of the Gut Microbiota in Spine Fusion Surgery Patients

Background: The microbiome has been identified as a contributor to bone quality. As skeletal health is critical to success of orthopedic surgery, the gut microbiome may be a modifiable factor associated with postoperative outcomes. For spine fusion surgery in particular, de novo bone formation and sufficient bone mineral density are essential for successful outcomes. Given the prevalence and complexity of these procedures, the identification of novel factors that may be related to operative success is important. Questions/purposes: We sought to investigate how the composition of the microbiota related to bone health in a focused spinal fusion surgery cohort. Methods: We investigated the composition of the microbiome in a cohort of 31 patients prior to spinal fusion surgery, as well as changes in the microbiome over 6 weeks postoperatively. Preoperative areal bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: Composition of gut microbiota differed among spinal fusion patients with low bone mass ( T-score ≤ −1.0) and those with normal BMD ( P = .03). There was no significant change in composition of the gut microbiota between preoperative evaluation and 6 weeks postoperatively. Conclusions: Our findings in this small sample suggest there may be a relationship between BMD and composition of the gut microbiome in patients who undergo spinal fusion surgery. Further work is needed to investigate these relationships as well as potential interventions to foster a favorable microbial composition in spinal fusion surgery patients.

Development and validation of an open-source tool for opportunistic screening of osteoporosis from hip CT images.

This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm3). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm2. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery.

The Effects of Dairy Product Supplementation on Bone Health Indices in Children Aged 3 to 18 Years: A Meta-Analysis of Randomized Controlled Trials.

Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm2), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm2), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm2), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm2), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health.

Association of trabecular bone score and bone mineral apparent density with the severity of bone fragility in children and adolescents with osteogenesis imperfecta: A cross-sectional study.

Osteogenesis imperfecta (OI) is a hereditary skeletal disease characterized by bone fragility. Areal bone mineral density (BMD), evaluated by dual-energy X-ray absorptiometry (DXA), is used to assess bone brittleness. The height-adjusted BMD Z-score (BMDHAZ) is calculated in children and adolescents with OI to reduce the confounding factor of short stature. However, even with the BMDHAZ, severity evaluation in children and adolescents with OI is challenging because certain abnormalities in bone quality cannot be accurately assessed by BMD analysis. The trabecular bone scores (TBS) and bone mineral apparent density (BMAD), which represent the structural integrity of bone and bone-size-associated BMD, respectively, are associated with fracture risk. Recently, age- and sex-specific reference ranges have been reported, enabling the calculation of Z-scores for children. To evaluate which density measurements show the highest correlation with fracture risk, we analyzed the associations between the Z-scores of TBS, BMAD, and BMDHAZ, fracture rate, and genetic variants. We retrospectively reviewed 42 participants with OI aged 5 to 20 years who underwent DXA. COL1A1/2 pathogenic variants were detected in 41 of the 42 participants. In participants with nonsense and frameshift variants (n = 17) resulting in haploinsufficiency and mild phenotype, the TBS Z-score was negatively correlated with fracture rate (FR) (r = -0.50, p = 0.042). In participants with glycine substitution (n = 9) causing the severe phenotype, the BMAD Z-scores were negatively correlated with FR (r = -0.74, p = 0.022). No correlation between the BMDHAZ and FR was observed in both groups. These findings suggest that the TBS and BMAD are useful in assessing children and adolescents with OI with specific genetic variants.

Persistent Deficits in Bone Quality in Treated Acromegaly: Evidence From Assessments of Microstructure.

Fractures are increased in patients with acromegaly, both before and after successful acromegaly treatment. Abnormalities of bone microstructure, which may underlie this fragility, are present in active acromegaly but to what extent these improve with acromegaly treatment or persist despite biochemical remission remains unclear. To examine these questions, we studied the effects of acromegaly treatment and remission on bone quality. Sixty-five women and men with acromegaly were studied. Subgroups underwent assessments of areal bone mineral density by dual x-ray absorptiometry, trabecular bone score (TBS), and volumetric bone mineral density, microarchitecture, stiffness and failure load of the distal radius and tibia by high-resolution peripheral quantitative tomography in a longitudinal study before and after acromegaly treatment and in a cross-sectional study in which patients were compared to sex-, age-, and body mass index-matched healthy controls. In the longitudinal study, significant increases in total, cortical, and trabecular densities at the radius and tibia and increased stiffness and failure load of the tibia occurred with acromegaly treatment. In the cross-sectional study, patients in biochemical remission after surgery had larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to controls. TBS did not change with acromegaly treatment but correlated with some microstructural parameters. We show, for the first time, that volumetric bone mineral density and microarchitecture of the peripheral skeleton improve with acromegaly treatment but remain abnormal in patients in remission after surgery compared to controls. These abnormalities, known to be associated with fractures in other populations, may play a role in the pathogenesis of persistent fragility in treated acromegaly.

Chronic hypoparathyroidism is associated with increased cortical bone density evaluated using high-resolution peripheral quantitative computed tomography.

This cross-sectional study aimed to assess bone mineral density (BMD), bone microarchitecture and fracture prevalence in women with chronic postsurgical hypoparathyroidism (hypoPT). Twenty-seven women with postsurgical hypoPT and 44 age-matched healthy women were included. Dual-energy X-ray absorptiometry was used to evaluate areal BMD and vertebral fracture assessment. High-resolution peripheral quantitative computed tomography assessed microarchitecture and volumetric BMD at the distal radius and tibia. Biochemical parameters, including fibroblast growth factor 23, C-terminal cross-linking telopeptide of type I collagen (ICTP), and procollagen type I N-terminal propeptide (P1NP), were also measured. Previous low-impact fractures were assessed and the 10-year fracture risk was estimated using the FRAX tool for the Brazilian population. No participant had prevalent clinical fractures, and both groups showed low risk for major and hip based on FRAX tool, but two hypoPT patients had moderate to severe morphometric vertebral fractures. Women with hypoPT had increased aBMD in the lumbar spine, femoral neck and total hip (p < 0.05) and higher cortical vBMD in the radius (p = 0.020) and tibia (p < 0.001). Trabecular bone was not affected. Both P1NP and ICTP suggested low bone turnover rates, but no significant correlation was observed between bone density or microstructure and any of the biochemical parameters. The prevalence of fragility fractures was low in HypoPT women and compatible with low fracture risk estimated by the FRAX tool. Patients had a higher aBMD and cortical vBMD than those of healthy control women, but the association with decreased bone turnover remains unclear.

Trabecular Bone Score in Assessing Bone Mineralization Status in Children with End- Stage Renal Disease: A Promising Tool

Areal-bone mineral density (aBMD) of lumbar-spine dual energy X-ray absorptiometry (DXA) scan is the most frequently used tool in evaluating BMD in pediatric patients, however its size dependency have significant impact on measurements accuracy in children with chronic kidney disease (CKD). This study aimed to evaluate the usefulness of trabecular bone score (TBS) computed during lumbar-spine DXA scan in assessing bone status in children on maintenance hemodialysis (HD). Ninety-three children on HD (aged 9–18 years) were subjected to lumbar-spine DXA-scan to obtain aBMD (g/cm2) and TBS.Z-scores of aBMD for chronological-age (aBMDZ-CA), height-age (aBMDZ-HA), and TBSZ-score were calculated using mean and SD values of 442 healthy controls. aBMD and TBS were significantly lower in short-for-age and normal height-for-age patients compared to the corresponding values of controls (p < 0.05 for all). Degraded vertebral microarchitecture (TBSZ-score < -2) was detected in 48% and 44% of male and female patients respectively. There were no significant differences in median TBSZ-score between short-for-age and normal height-for-age HD patients in male (p = 0.425) and in female (p = 0.316) patients. TBSZ-score correlated significantly with aBMDZ-CA (r = 0.234; p = 0.024) but not with aBMDZ-HA (r = 0.077; p = 0.462). Patients with history of fractures (5 patients only) had significantly lower TBS scores compared to those without fracture history (p = 0.016).Conclusion: TBS is significantly reduced in children on maintenance HD and is associated with increased fracture incidence. TBS has shown to be a promising tool in assessing bone quality (trabecular microarchitecture) in children with CKD being not size-dependent as is a-BMD, for further evaluation of its potential role in therapeutic and follow-up decisions.What is Known:• In children with CKD, bone demineralization starts as early as CKD stage 2, so assessment of bone health is mandatory for follow up and therapeutic decisions.• aBMD of lumbar-spine DXA scan is the most used tool in evaluating BMD in pediatric patients, however its size dependency have significant impact on measurements made in children with CKD.What is New:• TBS is significantly reduced in children on maintenance HD and associated with increased fracture incidence.• TBS has shown to be a promising tool in assessing bone quality (trabecular microarchitecture) in children with CKD being not size-dependent as is a-BMD.

Risk Factors Associated with Incident Vertebral Fractures in Steroid-treated Males with Duchenne Muscular Dystrophy.

Prevention of fractures is an unmet need in glucocorticoid (GC)-treated Duchenne muscular dystrophy. This study explored factors associated with incident vertebral fractures (VFs) to inform future fracture prevention efforts. VFs were evaluated prospectively at study baseline and 12 months on lateral spine radiographs in participants aged 4 to 25 years with Duchenne muscular dystrophy. Clinical factors were analyzed for their association with the change in Spinal Deformity Index (sum of the Genant-defined VF grades from T4 to L4) between baseline and 12 months. Thirty-eight males were evaluated (mean ± SD age at baseline 11.0 ± 3.6 years; mean ± SD GC duration at baseline 4.1 ± 3.1 years; 74% ambulatory). Nine of 38 participants (24%) had 17 incident VFs, of which 3/17 VFs (18%) were moderate/severe. Participants with 12-month incident VF had lower mean ± SD baseline lumbar spine areal bone mineral density Z-scores (-2.9 ± 1.0 vs -1.9 ± 1.1; P = .049) and lower total body less head areal bone mineral density Z-scores (-3.1 ± 1.2 vs -1.6 ± 1.7; P = .036). Multivariable linear regression showed that at least 1 VF at baseline (P < .001), a higher number of antecedent non-VF (P < .001), and greater bone age delay at baseline (P = .027) were significant predictors of an increase in the Spinal Deformity Index from baseline to 12 months. The observation that ≥ 1 prevalent VF and/or non-VF were the strongest predictors of incident VFs at 12 months supports the need for prevention of first fractures in this high-risk setting. Bone age delay, a marker of GC exposure, may assist in the prioritization of patients in efforts to prevent first fractures.

Computed Tomography Provides Improved Quantification of Trabecular Lumbar Spine Bone Loss Compared to Dual-Energy X-Ray Absorptiometry in Ovariectomized Sheep.

Early detection of osteoporosis using advanced imaging is imperative to the successful treatment and prevention of high morbidity fractures in aging patients. In this preclinical study, we aimed to compare dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to quantify bone mineral density (BMD) changes in the sheep lumbar spine. We also aimed to determine the relationship of BMD to microarchitecture in the same animals as an estimate of imaging modality precision. Osteoporosis was induced in 10 ewes via laparoscopic ovariectomy and administration of high-dose corticosteroids. We performed DXA and QCT imaging to measure areal BMD (aBMD) and trabecular volumetric BMD (Tb.vBMD)/cortical vBMD (Ct.vBMD), respectively, at baseline (before ovariectomy) and at 3, 6, 9, and 12 months after ovariectomy. Iliac crest bone biopsies were collected at each time point for micro-computed tomography (microCT) analysis; bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp) were reported. aBMD and Tb.vBMD both decreased significantly by 3 and 6 months (p < 0.05) compared with baseline, whereas no changes to Ct.vBMD were observed. Combined (Tb. and Ct.) vBMD was significantly correlated with aBMD at all time points (all p < 0.05). Additionally, greater significant correlations were found between BV/TV and Tb.vBMD at all five time points (R 2 = 0.54, 0.57, 0.66, 0.46, and 0.56, respectively) than with aBMD values (R 2 = 0.23, 0.55, 0.41, 0.20, and 0.19, respectively). The higher correlation of microCT values with QCT than with DXA indicates that QCT provides additional detailed information regarding bone mineral density changes in preclinical settings. Because trabecular bone is susceptible to rapid density loss and structural changes during osteoporosis, QCT can capture these subtle changes more precisely than DXA in a large animal preclinical model. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Changes in Bone Quality after Treatment with Etelcalcetide.

Secondary hyperparathyroidism is associated with osteoporosis and fractures. Etelcalcetide is an intravenous calcimimetic for the control of hyperparathyroidism in patients on hemodialysis. Effects of etelcalcetide on the skeleton are unknown. In a single-arm, open-label, 36-week prospective trial, we hypothesized that etelcalcetide improves bone quality and strength without damaging bone-tissue quality. Participants were 18 years or older, on hemodialysis ≥1 year, without calcimimetic exposure within 12 weeks of enrollment. We measured pretreatment and post-treatment areal bone mineral density by dual-energy X-ray absorptiometry, central skeleton trabecular microarchitecture by trabecular bone score, and peripheral skeleton volumetric bone density, geometry, microarchitecture, and estimated strength by high-resolution peripheral quantitative computed tomography. Bone-tissue quality was assessed using quadruple-label bone biopsy in a subset of patients. Paired t tests were used in our analysis. Twenty-two participants were enrolled; 13 completed follow-up (mean±SD age 51±14 years, 53% male, and 15% White). Five underwent bone biopsy (mean±SD age 52±16 years and 80% female). Over 36 weeks, parathyroid hormone levels declined 67%±9% ( P < 0.001); areal bone mineral density at the spine, femoral neck, and total hip increased 3%±1%, 7%±2%, and 3%±1%, respectively ( P < 0.05); spine trabecular bone score increased 10%±2% ( P < 0.001); and radius stiffness and failure load trended to a 7%±4% ( P = 0.05) and 6%±4% increase ( P = 0.06), respectively. Bone biopsy demonstrated a decreased bone formation rate (mean difference -25±4 µ m 3 / µ m 2 per year; P < 0.01). Treatment with etelcalcetide for 36 weeks was associated with improvements in central skeleton areal bone mineral density and trabecular quality and lowered bone turnover without affecting bone material properties. The Effect of Etelcalcetide on CKD-MBD (Parsabiv-MBD), NCT03960437.

Much lower prevalence and severity of spine degenerative changes among older Chinese women than among older Caucasian women and its implication for the interpretation of lumbar spine BMD T-score for Chinese women.

The prevalence and severity of spine degenerative changes have been noted to be lower among older Chinese women than among older Caucasian women. Spine degenerative changes associated with marginal osteophytosis, trabecular thickening, subchondral sclerosis, facet joint arthrosis, and disc space narrowing can all lead to artificially higher spine areal bone mineral density (BMD). The lower prevalence and severity of spine degeneration have important implications for the interpretation of spine areal BMD reading for Chinese women. With fewer contributions from spine degenerative changes, following natural aging, the declines of population group means of spine BMD and T-score are faster for Chinese women than for Caucasian women. While a cutpoint T-score ≤ -2.5 for defining spine densitometric osteoporosis is recommended for Caucasian women, for Chinese women the same cutpoint T-score of ≤ -2.5 inflates the estimated osteoporosis prevalence based on spine BMD measure. In addition to the use of an ethnicity-specific BMD reference database, a stricter cutpoint T-score for defining spine densitometric osteoporosis among older Chinese women should be applied.

Vitamin D supplementation for improving bone density in vitamin D–deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials

BackgroundVitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D–deficient children are unclear. ObjectivesThis study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D–deficient individuals. MethodsThis is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1–19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. ResultsEleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. ConclusionsClinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets).This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772