Lower Areal Bone Mineral Density Research Articles

Patella Fractures are Associated with Bone Fragility - A Retrospective Study.

Patella fractures are not typically considered osteoporotic fractures. We compared bone mineral density (BMD) and microstructure in elderly women from a multiethnic population-based study in New York City with any history of a patella fracture (n = 27) to those without historical fracture (n = 384) and those with an adult fragility forearm fracture (n = 28) using dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR-pQCT). Compared to those without fracture, women with patella fracture had 6.5% lower areal BMD (aBMD) by DXA only at the total hip (P=.007), while women with forearm fracture had lower aBMD at multiple sites and lower trabecular bone score (TBS), adjusted for age, body mass index (BMI), race and ethnicity (all P<.05). By HR-pQCT, adjusted radial total and trabecular (Tb) volumetric BMD (vBMD) and Tb number were 10-24% lower while Tb spacing was 12-23% higher (all P<.05) in the fracture groups versus women without fracture. Women with a forearm, but not a patella, fracture also had lower adjusted radial cortical (Ct) area and vBMD and 21.8% (P<.0001) lower stiffness vs. women without fracture. At the tibia, the fracture groups had 9.3-15.7% lower total and Tb vBMD (all P<.05) compared to the non-fracture group. Women with a forearm fracture also had 10.9, and 14.7% lower tibial Ct area and thickness versus those without fracture. Compared to women without fracture, tibial stiffness was 9.9 and 12% lower in the patella and forearm fracture groups, respectively (all P<.05). By HR-pQCT, the patella vs. forearm fracture group had 36% higher radial Tb heterogeneity (P<.05). In summary, women with patella fracture had Tb deterioration by HR-pQCT associated with lower tibial mechanical competence that was similar to those with fragility forearm fracture, a more universally accepted "osteoporotic" fracture. These data suggest patella fractures are associated with skeletal fragility and warrant skeletal evaluation.

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p&amp;lt;0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

5120 Contribution Of Proximal Femur Geometry And Bone Density Distribution To Hip Fragility In Adults ≥ 50yrs With Longstanding Type 1 Diabetes

Abstract Disclosure: F. Johannesdottir: None. C. D’Mello: None. A.B. Murthy: None. B. Zahedi: None. K. Engelke: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Introduction: Adults with type 1 diabetes (T1D) have a 6-fold increased risk of hip fracture, which is explained only in part by lower areal bone mineral density (aBMD) by DXA. We hypothesize that femoral geometry and regional bone deficits at the proximal femur contribute to higher hip fracture risk in older adults with T1D. Further, we determine the influence of age at T1D diagnosis on femoral bone density and structure. Methods: We enrolled 97 individuals with T1D and 53 non-diabetic controls (CON) as part of the T1D Bone Health Connection (BEACON) Study, an ongoing prospective study of adults aged ≥50 years. We obtained computed tomography (CT) scans of the proximal femur (in-plane pixel size 0.98x0.98 mm, 1.25 mm slice thickness) to measure total (Tt), trabecular (Tb) and cortical (Ct) volumetric BMD (vBMD); and volume (Vol) and Ct thickness (Th) in several regions, including total hip, femoral neck (FN), trochanter (TR) and intertrochanter (IT) (Medical Image Analysis Framework, University of Erlangen, Germany). We also assessed total hip and FN aBMD by DXA. We employed ANCOVA models to compare bone outcomes between T1D and controls with adjustment for age, height, and weight, stratified by sex. When comparing bone outcomes within T1D, we adjusted for age, height, weight, and sex. Differences are reported as % difference between the least-square means for the groups. Results: The average age of participants was 64±7 yrs, and similar between T1D and CON (p=0.21). Male T1D were shorter than male CON (173 cm vs 176 cm, p=0.05), but with similar weight (p=0.73). Female T1D were heavier than female CON (71 kg vs 64 kg, p=0.03). The T1D cohort included 50 men and 47 women with mean diabetes duration of 46±10 yrs, mean A1c 7.1±1.0%, and median age at onset 17 yrs (IQR:10-25). Among T1D, 31 (52% female) were diagnosed ≤ age 12. Among men, total hip and FN aBMD did not differ by group, but T1D had smaller FN Tt.Vol (9%) and FN width (8%) (p&amp;lt;0.05 for all). In contrast, there were no differences between T1D and CON in the female cohort, neither by DXA nor CT (p≥0.13). Of note, T1D men appeared to have more poorly controlled diabetes than women (29% of men vs 11% women had A1c ≥8%, p=0.03). Within T1D, those who were diagnosed ≤ age 12 had lower Tb.vBMD (16-18%) at the total hip, TR and IT regions (p&amp;lt;0.05) and tended to have lower Tb.vBMD (16%, p=0.06) at the neck compared to those diagnosed at a later age, but no differences in DXA aBMD (p&amp;gt;0.31). Conclusion: In sum, older men, but not women, with T1D showed some deficits in bone structure at the proximal femur. Adults with T1D who were diagnosed ≤ age 12 had trabecular bone deficits within the proximal femur. Additional studies are needed to identify mechanisms underlying the high hip fracture risk in T1D. Presentation: 6/1/2024

Co-morbid sarcopenia and low bone mineral density in young paediatric cancer survivors.

Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z-score in young paediatric cancer survivors with sarcopenia confirmed/probable. This cross-sectional study included 116 paediatric cancer survivors (12.1±3.3years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). 'No sarcopenia' was defined when muscle strength was >decile 2. 'Sarcopenia probable' was defined when muscle strength was ≤ decile 2 and ALMI Z-score was > -1.5 standard deviation (SD). 'Sarcopenia confirmed' was defined when muscle strength was ≤ decile 2 and ALMI Z-score ≤ -1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z-score < -1.0). Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (-1.2 [95% CI: -1.5 to -0.8] vs. 0.2 [-0.2 to 0.6], P<0.001), lumbar spine (-0.7 [-1.1 to -0.3] vs. 0.4 [0.0 to 0.8], P<0.001), total hip (-0.5 [-0.9 to -0.2] vs. 0.4 [0.1 to 0.8], P<0.001), and femoral neck (-1.0 [-1.4 to -0.6] vs. 0.1 [-0.3 to 0.4], P=0.001). Compared with survivors with sarcopenia probable, survivors with sarcopenia confirmed had significantly lower aBMD Z-score at total body (-1.2 [-1.5 to -0.8] vs. -0.2 [-0.7 to 0.4], P=0.009), total hip (-0.5 [-0.9 to -0.2] vs. 0.5 [-0.1 to 1.0], P=0.010), and femoral neck (-1.0 [-1.4 to -0.6] vs. 0.1 [-0.5 to 0.7], P=0.014). Survivors with sarcopenia confirmed were at higher risk of low aBMD Z-score at the total body (OR: 6.91, 95% CI: 2.31-24.15), total hip (OR: 2.98, 1.02-9.54), and femoral neck (OR: 4.72, 1.72-14.19), than those without sarcopenia. Survivors with sarcopenia probable were at higher risk of low aBMD Z-score at the total body (OR: 4.13, 1.04-17.60) than those without sarcopenia. Young paediatric cancer survivors with sarcopenia present higher risk of low aBMD. Resistance training-based interventions designed to mitigate osteosarcopenia in this population should be implemented at early stages.

Risk of low bone mineral density in young pediatric cancer survivors with sarcopenia.

10070 Background: Required treatments to cure pediatric cancer at such a young age increase the risk of later health-related complications. Early exposure to DNA damaging agents, during a vital period of active skeletal growth, interferes with accrual of bone mass. Treatments not only impair bone health, but also affect skeletal muscle function and mass. Long-term pediatric cancer survivors present these limitations due to myofibrillary atrophy caused by degradation of myosin heavy chain and decrease in myosin synthesis death. Muscle weakness (both muscle strength deficits and low lean mass hereafter referred to as sarcopenia) and low areal bone mineral density (aBMD) have been observed to coexist in adult survivors of paediatric cancer. However, in young pediatric cancers survivors, associations between sarcopenia and low aBMD are not well described. Therefore, this study aimed to examine the risk of low aBMD in young pediatric cancer survivors with sarcopenia confirmed/probable, compared to not having sarcopenia. Methods: This cross-sectional study included 116 pediatric cancer survivors (12.1±3.3 years old; 42% female) enrolled on a randomized controlled trial designed to improve bone health (iBoneFIT project). Handgrip strength was used to assessed muscle strength. Dual-energy X-ray absorptiometry estimated aBMD (g/cm2) at the total body (less head), lumbar spine, total hip and femoral neck, and appendicular lean mass index (ALMI, kg/m2). Sarcopenia status was determined using age and sex specific international reference data from a healthy population. “No sarcopenia” was defined when muscle strength was &gt;decile 2. “Sarcopenia probable” was defined when muscle strength was ≤decile 2 and ALMI Z-score was &gt; -1.5 standard deviation (SD). “Sarcopenia confirmed” was defined when muscle strength was ≤decile 2 and ALMI Z-score ≤-1.5 SD. Logistic regression, adjusted for time from treatment completion and radiation exposure, was used to evaluate the risk of low aBMD (age-, sex- and race-specific aBMD Z-score &lt; -1.0) by sarcopenia status. Results: More than one-third of survivors met criteria for sarcopenia confirmed (37.9%); 19.0% met criteria for sarcopenia probable. Survivors with sarcopenia confirmed had higher risk of low aBMD at the total body (odd ratio [OR]: 6.91, 95% confidence interval [CI]: 2.31-24.15), total hip (OR: 2.98, 95% CI: 1.02-9.54) and femoral neck (OR: 4.72, 95% CI: 1.72-14.19) than those without sarcopenia. Survivors with sarcopenia probable had higher risk of having low aBMD only at the total body (OR: 4.13, 95% CI: 1.04-17.60) than those without sarcopenia. Conclusions: Over one-third of young paediatric cancer survivors presented sarcopenia confirmed with higher risk of low aBMD. These findings suggest that interventions to mitigate osteosarcopenia in this population should be implemented at early stages after treatment completion.

Effect of Allele-Specific Clcn7G213R siRNA Delivered Via a Novel Nanocarrier on Bone Phenotypes in ADO2 Mice on 129S Background.

Autosomal dominant osteopetrosis type 2 (ADO2) is a rare inherited bone disorder characterised by dense but brittle bones. It displays striking phenotypic variability, with the most severe symptoms, including blindness and bone marrow failure. Disease management largely relies on symptomatic treatment since there is no safe and effective treatment. Most ADO2 cases are caused by heterozygous loss-of-function mutations in the CLCN7 gene, which encodes an essential Cl-/H+ antiporter for proper bone resorption by osteoclasts. Thus, siRNA-mediated silencing of the mutant allele is a promising therapeutic approach, but targeting bone for first-in-human translation remains challenging. Here, we demonstrate the utility of silicon-stabilised hybrid lipid nanoparticles (sshLNPs) as a next-generation nucleic acid nanocarrier capable of delivering allele-specific siRNA to bone. Using a Clcn7G213R knock-in mouse model recapitulating one of the most common human ADO2 mutations and based on the 129S genetic background (which produces the most severe disease phenotype amongst current models), we show substantial knockdown of the mutant allele in femur when siRNA targeting the pathogenic variant is delivered by sshLNPs. We observed lower areal bone mineral density in femur and reduced trabecular thickness in femur and tibia, when siRNA-loaded sshLNPs were administered subcutaneously (representing the most relevant administration route for clinical adoption and patient adherence). Importantly, sshLNPs have improved stability over conventional LNPs and enable 'post hoc loading' for point-of-care formulation. The treatment was well tolerated, suggesting that sshLNP-enabled gene therapy might allow successful clinical translation of essential new treatments for ADO2 and potentially other rare genetic bone diseases.

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. The mean age of the patients was 45.5 ± 9.3years with a lag of 8.3 ± 7.2years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Fracture risk based on high-resolution peripheral quantitative computed tomography measures does not vary with age in older adults-the bone microarchitecture international consortium prospective cohort study.

Fracture risk increases with lower areal bone mineral density (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) dual energy X-ray absorptiometry (DXA) which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures.

Longitudinal Assessment of Bone Mineral Density in Women Living With and Without HIV Across Reproductive Phases.

Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states. Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites. This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables. Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (β: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (β: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (β: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (β: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (β: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss. HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age.

Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors: The iBoneFIT project

BackgroundPediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density (aBMD). However, the prevalence of muscle strength deficits is not well documented, and the associations of muscle strength with aBMD are unknown in this population. Therefore, this study aimed to investigate the prevalence of upper- and lower-body muscle strength deficits and to examine the associations of upper- and lower-body muscle strength with age-, sex, and race-specific aBMD Z-scores at the total body, total hip, femoral neck, and lumbar spine. MethodsThis cross-sectional study included 116 pediatric cancer survivors (12.1 ± 3.3 years old, mean ± SD; 42.2% female). Upper- and lower-body muscle strength were assessed by handgrip and standing long jump test, respectively. Dual‑energy X‑ray absorptiometry was used to measure aBMD (g/cm2). Associations between muscle strength and aBMD were evaluated in multivariable linear regression models. Logistic regression was used to evaluate the contribution of muscle strength (1-decile lower) to the odds of having low aBMD (Z-score ≤ 1.0). All analyses were adjusted for time from treatment completion, radiotherapy exposure, and body mass index. ResultsMore than one-half of survivors were within the 2 lowest deciles for upper- (56.9%) and lower- body muscle strength (60.0%) in comparison to age- and sex-specific reference values. Muscle strength deficits were associated with lower aBMD Z-scores at all sites (B = 0.133–0.258, p = 0.001–0.032). Each 1-decile lower in upper-body muscle strength was associated with 30%–95% higher odds of having low aBMD Z-scores at all sites. Each 1-decile lower in lower-body muscle strength was associated with 35%–70% higher odds of having low aBMD Z-scores at total body, total hip, and femoral neck. ConclusionMuscle strength deficits are prevalent in young pediatric cancer survivors, and such deficits are associated with lower aBMD Z-scores at all sites. These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.

Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.

Relationship of sarcopenia with bone geometry and mass among postmenopausal women.

The aim of this study was to verify whether sarcopenia and its components are associated with hip areal bone mineral density (aBMD) and geometry in postmenopausal women (PW). In this cross-sectional study, appendicular bone-free lean mass (aLM) and hip bone mass and geometry were measured using dual-energy x-ray emission absorptiometry (DXA). Muscle power and strength were measured by five times Sit-to-Stand Test (5-STS) and dynamometry, respectively, in 175 PW. Sarcopenia was identified as low aLM plus low muscle strength or low muscle power. Multiple linear regression (covaried by age, smoking, hormonal therapy, and diseases) was used to determine the relationship between sarcopenia and bone geometry and mass. The results are presented as mean differences between groups. Dynamometry, five times Sit-to-Stand Test, and aLM indicated positive associations (P < 0.05) with most indicators of bone mass and geometry. Sarcopenia, applying low muscle strength or low muscle power, was negatively associated with femoral neck width (-0.2 mm, P = 0.001), cortical thickness of femoral calcar (-0.6 mm, P = 0.043), subtrochanteric cortical thickness (-1.2 mm, P = 0.002), femoral neck cross-sectional area (-19.5 mm2, P < 0.001), cross-section moment of inertia (-2,244 mm4, P < 0.001), section modulus (-115 mm3, P < 0.001), femoral neck aBMD (-0.1 g/cm2, P = 0.002), upper femoral neck aBMD (-0.1 g/cm2, P = 0.003), lower femoral neck aBMD (-0.1 g/cm2, P = 0.016), and trochanteric aBMD (-0.1 g/cm2, P = 0.035). Thus, muscle mass, strength and power, alone or in combination (ie, sarcopenia), are associated with low aBMD, impaired bone geometry, and, therefore, bone strength in PW. These measures may help identify PW at risk of hip fractures.

Altered bone and body composition in children and adolescents with confirmed prenatal alcohol exposure.

Prenatal alcohol exposure can contribute to long term adverse health outcomes. Development of the skeletal system begins at the early embryonic stage and continues into early adulthood but the effect of prenatal alcohol exposure on skeletal growth is relatively unexplored in a clinical population. Here, we performed dual X-ray absorptiometry to examine bone, fat, and muscle accrual in children and adolescents diagnosed with, or at risk of, fetal alcohol spectrum disorders (FASDs). Children (aged 4-9years) with FASD or at risk of FASD (n=10) had similar growth to age matched controls (n=27). By adolescence (aged ≥10years), those with FASDs (n=13) were shorter and had lower areal bone mineral density and lean tissue mass than typically developing peers (n=29). Overall, adolescents diagnosed with FASDs had greater odds of impairments to bone and body composition. These findings highlight the importance of early FASD diagnosis and appropriate post-diagnostic medical follow-up to enable timely, effective interventions to optimize bone and body composition during paediatric growth.

High prevalence of vertebral deformity in tumor-induced osteomalacia associated with impaired bone microstructure.

Patients with tumor-induced osteomalacia (TIO) often suffer from irreversible height loss due to vertebral deformity. However, the prevalence of vertebral deformity in TIO patients varies among limited studies. In addition, the distribution and type of vertebral deformity, as well as its risk factors, remain unknown. This study aimed to identify the prevalence, distribution, type and risk factors for vertebral deformity in a large cohort of TIO patients. A total of 164 TIO patients were enrolled in this retrospective study. Deformity in vertebrae T4-L4 by lateral thoracolumbar spine radiographs was evaluated according to the semiquantitative method of Genant. Bone microstructure was evaluated by trabecular bone score (TBS) and high-resolution peripheral QCT (HR-pQCT). Ninety-nine (99/164, 60.4%) patients had 517 deformed vertebrae with a bimodal pattern of distribution (T7-9 and T11-L1), and biconcave deformity was the most common type (267/517, 51.6%). Compared with patients without vertebral deformity, those with vertebral deformity had a higher male/female ratio, longer disease duration, more height loss, lower serum phosphate, higher bone turnover markers, lower TBS, lower areal bone mineral density (aBMD), lower peripheral volumetric BMD (vBMD) and worse microstructure. Lower trabecular vBMD and worse trabecular microstructure in the peripheral bone and lower spine TBS were associated with an increased risk of vertebral deformity independently of aBMD. After adjusting for the number of deformed vertebrae, we found little difference in clinical indexes among the patients with different types of vertebral deformity. However, we found significant correlations of clinical indexes with the number of deformed vertebrae and the spinal deformity index. We reported a high prevalence of vertebral deformity in the largest cohort of TIO patients and described the vertebral deformity in detail for the first time. Risk factors for vertebral deformity included male sex, long disease duration, height loss, abnormal biochemical indexes and bone impairment. Clinical manifestation, biochemical indexes and bone impairment were correlated with the number of deformed vertebrae and degree of deformity, but not the type of deformity.

Young Adult Male Patients With Childhood-onset IBD Have Increased Risks of Compromised Cortical and Trabecular Bone Microstructures.

Young adults with childhood-onset inflammatory bowel disease (IBD) have increased risks of low areal bone mineral density and low skeletal muscle mass. Volumetric BMD (vBMD), bone geometry and microstructures, in addition to possible associations with skeletal muscle index (SMI) and physical exercise have been scarcely studied in this patient group. In total, 49 young adult male patients with childhood-onset IBD and 245 age- and height-matched young adult male controls were scanned with high-resolution peripheral quantitative computed tomography. Bone geometry, vBMD, and bone microstructures were calculated as median values and compared between the patients and controls. Multivariable linear regression analyses were performed to determine the independent associations among IBD diagnosis, SMI (kg/m2), and physical exercise. The group of young adult patients had, in comparison with the controls, significantly smaller median cortical area (126.1 mm2 vs151.1 mm2, P < .001), lower median total vBMD (296.7 mg/cm3 vs 336.7 mg/cm3, P < .001), and lower median cortical vBMD (854.4 mg/cm3 vs 878.5 mg/cm3, P < .001). Furthermore, the patients compared with the controls had lower median trabecular volume fraction (16.8% vs 18.2%, P < .001) and thinner median trabeculae (0.084 mm vs 0.089 mm, P < .001). The differences between the patients with IBD and controls persisted in multivariable analyses that included adjustments for SMI and physical exercise. Young adult men with childhood-onset IBD are at increased risk of having reduced bone quality in both the cortical and trabecular bone structures compared with normative matched controls.

Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study

Anorexia nervosa (AN) increases the risk of impaired bone health, low areal bone mineral density (aBMD), and subsequent fractures. This prospective study investigated the long-term effects of bone and mineral metabolism on bone and biomarkers in 22 women with AN. Body composition and aBMD were measured by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography. Total and free 25-hydroxyvitamin D (25OHD), C-terminal collagen cross-links (CTX), osteocalcin, bone-specific alkaline phosphatase (BALP), leptin, sclerostin, and oxidized/non-oxidized parathyroid hormone (PTH) were analyzed before and after 12weeks of intensive nutrition therapy and again 3years later. An age-matched comparison group of 17 healthy women was recruited for the 3-year follow-up. Body mass index (BMI) and fat mass increased from baseline to 3years in women with AN. Sclerostin decreased during nutrition therapy and further over 3years, indicating reduced bone loss. CTX was elevated at baseline and after 12weeks but decreased over 3years. BALP increased during nutrition therapy and stabilized over 3years. Free 25OHD was stable during treatment but decreased over 3years. Non-oxidized PTH was stable during treatment but increased over 3years. Trabecular volumetric BMD in AN patients decreased during the first 12weeks and over 3years despite stable BMI and bone biomarkers implying increased BMD. Our findings highlight the importance of early detection and organized long-term follow-up of bone health in young women with a history of AN.

The effect of low-intensity whole-body vibration with or without high-intensity resistance and impact training on risk factors for proximal femur fragility fracture in postmenopausal women with low bone mass: study protocol for the VIBMOR randomized controlled trial

BackgroundThe prevailing medical opinion is that medication is the primary (some might argue, only) effective intervention for osteoporosis. It is nevertheless recognized that osteoporosis medications are not universally effective, tolerated, or acceptable to patients. Mechanical loading, such as vibration and exercise, can also be osteogenic but the degree, relative efficacy, and combined effect is unknown. The purpose of the VIBMOR trial is to determine the efficacy of low-intensity whole-body vibration (LIV), bone-targeted, high-intensity resistance and impact training (HiRIT), or the combination of LIV and HiRIT on risk factors for hip fracture in postmenopausal women with osteopenia and osteoporosis.MethodsPostmenopausal women with low areal bone mineral density (aBMD) at the proximal femur and/or lumbar spine, with or without a history of fragility fracture, and either on or off osteoporosis medications will be recruited. Eligible participants will be randomly allocated to one of four trial arms for 9 months: LIV, HiRIT, LIV + HiRIT, or control (low-intensity, home-based exercise). Allocation will be block-randomized, stratified by use of osteoporosis medications. Testing will be performed at three time points: baseline (T0), post-intervention (T1; 9 months), and 1 year thereafter (T2; 21 months) to examine detraining effects. The primary outcome measure will be total hip aBMD determined by dual-energy X-ray absorptiometry (DXA). Secondary outcomes will include aBMD at other regions, anthropometrics, and other indices of bone strength, body composition, physical function, kyphosis, muscle strength and power, balance, falls, and intervention compliance. Exploratory outcomes include bone turnover markers, pelvic floor health, quality of life, physical activity enjoyment, adverse events, and fracture. An economic evaluation will also be conducted.DiscussionNo previous studies have compared the effect of LIV alone or in combination with bone-targeted HiRIT (with or without osteoporosis medications) on risk factors for hip fracture in postmenopausal women with low bone mass. Should either, both, or combined mechanical interventions be safe and efficacious, alternative therapeutic avenues will be available to individuals at elevated risk of fragility fracture who are unresponsive to or unwilling or unable to take osteoporosis medications.Trial registrationAustralian New Zealand Clinical Trials Registry (www. anzctr.org.au) (Trial number ANZCTR12615000848505, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id = 368962); date of registration 14/08/2015 (prospectively registered). Universal Trial Number: U1111-1172-3652.

Investigation of the Factors Affecting Bone Mineral Density in Children with Celiac Disease.

PurposeChildren with celiac disease (CD) are at an increased risk of low bone mineral density (BMD) owing to malabsorption of fat-soluble vitamins, inflammation, and malnutrition. This study aimed to determine the prevalence and risk factors for low BMD in Iranian children with CD.MethodsThis prospective cohort study examined 149 Iranian children with CD between 2011 and 2018 at Zabol University of Medical Sciences. BMD was measured using dual-energy X-ray absorptiometry. Demographic, clinical, and laboratory data were collected from patients’ medical records. Logistic regression analysis was performed to identify the factors associated with low areal BMD (BMD-Z <−2) in the lumbar spine and femoral neck. Descriptive data were analyzed using the mean, standard deviation, and relative frequency. Data were analyzed using the chi-square test, t-test, and analysis of variance.ResultsOf the 149 children with CD, 27.5% had osteoporosis. The mean body mass index (BMI) Z score was −1.28±1.2. Lower BMI was associated with a higher likelihood of BMD-Z (odds ratio 2.17; p≤0.05).ConclusionOverall, the findings of this study showed that there was no correlation among Marsh classification, presence of specific human leukocyte antigens, and low BMD in Iranian children with CD. BMI can be a predictor of bone density in children with CD and may be applied clinically in early screenings to evaluate the bone health status in these children.

Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Trial.

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n= 33), 12 months of risedronate ("Risedronate") (n= 33), or double placebo ("Placebo") (n= 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p= 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p< 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p< 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR).

The skeletal consequences of epidural steroid injections: a literature review.

Approximately nine million epidural steroid injections (ESIs) are administered annually in the United States to treat radicular back pain. ESIs often provide pain relief and functional improvement. While the overall incidence of adverse events resulting from ESIs is low, their effects on the skeleton are poorly understood. This is an important consideration given the profound skeletal impact of other forms of glucocorticoids. Ovid MEDLINE and PubMed search results since 2010, including older, frequently referenced publications were reviewed. Systemic absorption of glucocorticoids occurs after ESI, which can cause hyperglycemia and endogenous cortisol suppression. The majority of studies investigating the skeletal effects of ESIs are retrospective. Several have found a relationship between low areal bone mineral density (BMD) by dual-energy x-ray absorptiometry and ESI exposure, but this finding is not uniform. Recently a dose-response relationship between ESI exposure and low spine volumetric BMD by computed tomography has been reported. Few studies have investigated the relationship between ESI exposure and fracture risk. Results of these studies are conflicting, and most have not been adequately powered to detect fracture outcomes. While evidence is limited, studies suggest that ESIs may cause bone loss, particularly those investigating volumetric BMD. Larger doses appear to confer greater risk. Further prospective studies are needed to investigate the relationship between ESI and fracture risk. Better understanding of the skeletal consequences of ESIs will help foster strategies to prevent bone loss in the growing population of patients receiving this treatment.