Hip Bone Mineral Density Z-scores Research Articles

Association between Low Bone Mineral Density and Pain in a Prospective Cohort of Adults with Sickle Cell Disease: Preliminary Results from the SCD Bone Pain Study

Background: Osteonecrosis (ON), a prevalent skeletal complication of sickle cell disease (SCD), typically associates with severe chronic pain, frequent acute care utilization, and permanent disability. We previously showed that low bone mineral density (BMD) independently associates with hip ON and chronic pain in a pediatric SCD cohort. We now present preliminary data on the association between low BMD and pain in a prospective cohort of adults enrolled in the SCD Bone Pain Study (NCT05283148). Methods: Written informed consent was obtained from all participants, who were recruited from ambulatory adults with SCD seen at the University of California Davis Comprehensive Cancer Center. All participants underwent dual-energy X-ray absorptiometry (DXA) scans of their lumbar spine, left hip, and left forearm. Vertebral fractures were assessed by thoracolumbar morphometry in the DXA scanner. All participants also completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact questionnaire. We used linear regression to evaluate the association between ASCQ-Me pain scores and low BMD (categorically defined as BMD Z-score ≤ -2 at any DXA site). We also used linear regression to determine the association between ASCQ-Me pain scores and continuous total hip and lumbar spine BMD Z-scores. Lastly, we evaluated the impact of other covariates on pain scores, with low BMD or BMD Z-scores included in the least absolute shrinkage and selection operator (LASSO, no shrinkage). Results: Thirty adults (median age 34.5 years [20-67 years]) completed the study between Nov 2022-Jul 2023. Baseline characteristics are summarized in Table 1. There was a borderline significant association between low BMD and lower (worse) pain scores (p=0.077). Continuous BMD Z-scores of the total hip (p=0.081) and lumbar spine (p=0.024) were independently associated with higher (better) pain scores. In addition to low BMD, only white blood cell count (WBC), indirect bilirubin, and vitamin D were identified as possible covariates (all had non-zero coefficients in LASSO analysis). Low BMD was significantly associated with pain (p=0.024), even after adjusting for WBC, indirect bilirubin, and vitamin D (Table 2). Similarly, we found that higher hip (p=0.059) and lumbar (p=0.027) BMD Z-scores were associated with higher (better) pain scores, despite adjusting for the same confounders. Discussion: We found low BMD in 12 of 30 (40%) adults enrolled in the SCD Bone Pain Study. Like other chronic hemolytic anemias, compensatory increased erythropoiesis leads to trabeculae degradation, cortical bone thinning, and eventual low bone mass. Lumbar vertebrae comprises mostly of trabecular bone, while the hip joint has mostly cortical bone. This might explain why mean lumbar BMD Z-scores were lower than hip BMD Z-scores (Table 1), and why lumbar spine BMD Z-scores directly and significantly correlated with pain scores (Table 2). These preliminary data suggest that pain is more prevalent in SCD adults with low BMD than those with normal BMD as we previously reported in a pediatric SCD cohort. Pain scores decrease (worsen) with increasing WBC, which suggests an inflammatory component to chronic SCD pain. Contrary to expectation, higher indirect bilirubin (a marker of increased hemolysis) significantly correlated with higher (better) pain scores. Similarly, higher vitamin D (a proxy for bone health) correlated with lower (worse) pain scores, though this association was non-significant. The reason(s) for these counterintuitive associations between pain scores, indirect bilirubin, and vitamin D levels is currently unknown. Limitations include a small sample size, though using the LASSO method for multivariate regression adjusted for this. Further, low BMD causality could not be determined at this time. Recruitment is ongoing with an enrollment target of 50 adults with SCD by Nov 2023. Analysis are ongoing to determine if SCD-modifying therapies will impact the association between low BMD and pain. Bone biomarker studies are also pending. Further, the thoracolumbar morphometry is still undergoing radiologic review, so we can further assess how vertebral compression fractures (i) correlate with pain scores, and/or (ii) attenuate the association between low BMD and pain. Identifying and treating risk factors for low BMD may alleviate bone pain and potentially improve quality of life for all people with SCD.

Lrp5 p.Val667Met Variant Compromises Bone Mineral Density and Matrix Properties in Osteoporosis.

Early-onset osteoporosis (EOOP) has been associated with several genes, including LRP5, coding for a coreceptor in the Wnt pathway. Variants in LRP5 were also described in osteoporosis pseudoglioma syndrome, combining severe osteoporosis and eye abnormalities. Genomewide-association studies (GWAS) showed that LRP5 p.Val667Met (V667M) variant is associated with low bone mineral density (BMD) and increased fractures. However, despite association with a bone phenotype in humans and knockout mice, the impact of the variant in bone and eye remains to be investigated. Here, we aimed to evaluate the bone and ocular impact of the V667M variant. We recruited 11 patients carrying the V667M variant or other loss-of-function variants of LRP5 and generated an Lrp5 V667M mutated mice. Patients had low lumbar and hip BMD Z-score and altered bone microarchitecture evaluated by HR-pQCT compared with an age-matched reference population. Murine primary osteoblasts from Lrp5 V667M mice showed lower differentiation capacity, alkaline phosphatase activity, and mineralization capacity in vitro. Ex vivo, mRNA expression of Osx, Col1, and osteocalcin was lower in Lrp5 V667M bones than controls (all p < 0.01). Lrp5 V667M 3-month-old mice, compared with control (CTL) mice, had decreased BMD at the femur (p < 0.01) and lumbar spine (p < 0.01) with normal microarchitecture and bone biomarkers. However, Lrp5 V667M mice revealed a trend toward a lower femoral and vertebral stiffness (p = 0.14) and had a lower hydroxyproline/proline ratio compared with CTL, (p = 0.01), showing altered composition and quality of the bone matrix. Finally, higher tortuosity of retinal vessels was found in the Lrp5 V667M mice and unspecific vascular tortuosity in two patients only. In conclusion, Lrp5 V667M variant is associated with low BMD and impaired bone matrix quality. Retinal vascularization abnormalities were observed in mice. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

DXA-derived advanced hip analysis and the trabecular bone score in end-stage kidney disease secondary to type 1 diabetes.

Patients with end-stage kidney disease (ESKD) caused by type 1 diabetes mellitus (T1DM) have a heightened fracture risk. Bone mineral density (BMD) may predict fracture less accurately in ESKD than in patients with chronic kidney disease (CKD) stages 1-3b or the general population. Alternate, readily available imaging modalities are needed to improve ESKD fracture risk assessment. This study aimed to assess dual-energy X-ray absorptiometry (DXA)-derived BMD, the trabecular bone score (TBS) and advanced hip analysis parameters in patients with ESKD due to T1DM and to compare their results with those of patients with ESKD from other causes. We compared the DXA-derived TBS, hip cortical thickness (CT) and femoral neck (FN) buckling ratio (BR), an index of FN stability, of patients with T1DM and ESKD undergoing simultaneous pancreas kidney transplantation, patients with ESKD from other causes receiving kidney transplants and population reference ranges. Of 227 patients with ESKD, 28% had T1DM and 65% were male. Compared with other ESKD patients, patients with T1DM were younger (42 ± 7.7 vs 51 ± 13.8 years), had shorter dialysis duration (24.4 ± 21 vs 42.6 ± 40 months), had higher HbA1c (7.9 ± 1.57% vs 5.4 ± 0.95%) and had lower BMI (25 ± 6 vs 27 ± 5 kg/m2). They had lower spine, hip and UD radius BMD Z-scores (all P ≤ 0.001), TBS (1.33 ± 0.12 vs 1.36 ± 0.12; P = 0.05), CT at the FN (P = 0.03), calcar (P = 0.006) and shaft (P < 0.001) and higher BR (10.1±7.1 vs 7.7±4; P = 0.006). All ESKD parameters were lower than population-based reference ranges (P < 0.001). Adjusting for age, sex, dialysis vintage and weight, prevalent vertebral fractures in patients with T1DM and ESKD were associated with higher BR (odds ratio (OR): 3.27 (95% CI: 1.19-8.92), P = 0.002) and lower FN CT (OR: 3.70 (95% CI: 1.13-12.50)). Patients with ESKD and T1DM have reduced TBS, reduced CT and increased BR compared with other ESKD patients. Prospective study of these parameters is warranted to determine their utility in fracture risk prediction and management. Patients with ESKD and T1DM have an elevated fracture risk due to decreased bone strength. As an adjunct to BMD, evaluating dual-energy X-ray absorptiometry parameters that incorporate structural change may have greater value in patients with ESKD and T1DM than in the general population. In this study, patients with ESKD due to T1DM had lower BMD, lower trabecular bone scores, more severe loss of CT and higher BR than other patients with ESKD and people from the general population. Both lower CT and higher BR were associated with prevalent vertebral fractures in patients with T1DM and ESKD. Changes to these parameters should be evaluated for incident fracture prediction.

Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study

BackgroundIndividuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes.MethodsWe analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering.ResultsOf 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM βosteophyte = 0.30 [0.01, 0.58], p = 0.019 and βJSN = 0.10 [0.01, 0.18], p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98], p = 0.032).ConclusionsHBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation.

Bone mineral density in Canadian children with severe haemophilia A or B: a cross-sectional study

Abstract Background Previous research has shown that bone mineral density (BMD), a measure of bone strength, may be lower among people with haemophilia. However, the majority of this research has been done in adults and in countries where the treatment for haemophilia differs from the standard of care in Canada, and there is a lack of paediatric data. Aims The primary objective of this study was to determine whether Canadian children and youth with severe haemophilia A and B have BMD similar to healthy controls matched for height, age and weight (HAW-score). Secondary objectives included the exploration of any association between BMD and the following variables: factor replacement regimen, Hemophilia Joint Health Score (HJHS), bleeding history, physical activity level, and dietary intake of calcium, vitamin D, vitamin K and protein. Methods A cross-sectional observational study was designed to determine the BMD of children with severe haemophilia A and B in Canada. Ethical approvals were obtained from participating institutions. Thirty-eight participants aged 3–18 with severe haemophilia A and B were recruited from two treatment centres in Canada. Subjects underwent dual-energy X-ray absorptiometry (DXA) scan, and data was collected from regular clinic visit to identify factor replacement regimen, HJHS, and number of joint bleeds over the lifespan. Physical activity level and dietary intake of calcium, vitamin D, vitamin K and protein were identified using self-report questionnaires. Results Participants showed a mean spine BMD Z-score and HAW-score higher than controls, with no participants showing a spine Z-score or HAW-score of &lt;0. Hip BMD score was within normal range, and 2 participants had a Z-score and HAW-score of &lt;−2. Total body BMD score was lower than controls, with 6 participants having a Z-score of &lt;−2.0, and 3 participants having a HAW-score of &lt;−2.0. Factor replacement regimen, HJHS, calcium intake, and physical activity level had no relationship to BMD Z-score or HAW-score. Low intake of vitamin D was associated with a low hip and spine BMD Z-score and HAW-score. Participants with a HJHS joint score greater than 0 had a higher total body HAW-score than those who had a joint score of 0. Conclusion Canadian children with severe haemophilia A and B demonstrate differences in spine and total body BMD from height-, age-, and weight-matched controls, where spine BMD is higher than controls and total body BMD is lower than controls. Studies with a larger sample size are needed to clarify the status of BMD in children with haemophilia treated with primary prophylaxis.

Bone mineral density improves during 2 years of treatment with bisphosphonates in patients with ankylosing spondylitis.

AimsTo evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumour necrosis factor‐α inhibitors or receiving conventional treatment. Secondly, to explore the development of radiographic vertebral fractures.MethodsPatients from the Groningen Leeuwarden AS cohort receiving bisphosphonates based on clinical indication and available 2‐year follow‐up BMD measurements were included. BMD of lumbar spine (L1–L4) and hip (total proximal femur) were measured using dual‐energy X‐ray absorptiometry. Spinal radiographs (Th4–L4) were scored for vertebral fractures according to the Genant method.ResultsIn the 20 included patients (median 52 years, 14 males), lumbar spine and hip BMD Z‐scores increased significantly; median from −1.5 (interquartile range [IQR] −2.2 to 0.4) to 0.1 (IQR −1.5 to 1.0); P < .001 and median from −1.0 (IQR −1.6 to −0.7) to −0.8 (IQR −1.2 to 0.0); P = .006 over 2 years, respectively. In patients also treated with tumour necrosis factor‐α inhibitors (n = 11), lumbar spine and hip BMD increased significantly (median 2‐year change +8.6% [IQR 2.4 to 19.6; P = .009] and +3.6% [IQR 0.7–9.0; P = .007]). In patients on conventional treatment (n = 9), lumbar spine BMD increased significantly (median 2‐year change +3.6%; IQR 0.7 to 9.0; P = .011) and no improvement was seen in hip BMD (median −0.6%; IQR −3.1 to 5.1; P = .61). Overall, younger AS males with limited spinal radiographic damage showed most improvement in lumbar spine BMD. Four mild radiographic vertebral fractures developed in 3 patients and 1 fracture increased from mild to moderate over 2 years in postmenopausal women and middle‐aged men.ConclusionThis explorative observational cohort study in AS showed that 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements significantly improves lumbar spine BMD. Mild radiographic vertebral fractures still occurred.

Individuals with high bone mass have increased progression of radiographic and clinical features of knee osteoarthritis

High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR=1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (β=7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

Prolonged Amenorrhea and Low Hip Bone Mineral Density in Women Living With HIV-A Controlled Cross-sectional Study.

Women living with HIV (WLWH) have higher rates of prolonged secondary amenorrhea (no flow for ≥1 year) than HIV-negative women. Both having amenorrhea and being HIV positive are associated with lower areal bone mineral density (BMD). However, their combined BMD effects remain unclear. Therefore, we investigated prolonged amenorrhea and BMD in WLWH and controls. This cross-sectional study enrolled WLWH and HIV-negative control women aged 19-68 years of similar backgrounds. We assessed BMD (Hologic; as age- and ethnicity-matched Z-scores) in the Children and women: AntiRetrovirals and Markers of Aging cohort. Participants were stratified by amenorrhea history defined as past/present lack of menses for ≥1 year at age 45 and younger and not because of surgery, breastfeeding, pregnancy, or hormonal contraception. Hip and spine Z-scores by amenorrhea/no amenorrhea used linear models with multivariable analysis for relationships within WLWH. WLWH (N = 129) were similar to controls (N = 129) in age, body mass index, ethnicity, and substance use. Among WLWH, 21% experienced prolonged amenorrhea vs. 9% in controls. WLWH had significantly lower total hip (mean ± SD: -0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (-0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores than controls. Amenorrhea was independently associated with hip (P = 0.01) but not spine (P = 0.94) BMD by multivariable linear regression. WLWH with amenorrhea had lower hip Z-scores (-0.8 ± 0.9) than those without (-0.3 ± 0.8; P = 0.01). They also had higher rates of substance use, smoking, opioid therapy, hepatitis C coinfection, and lower CD4 nadir. WLWH had higher rates of prolonged amenorrhea and lower BMD than controls. WLWH with amenorrhea experienced lower hip BMD Z-scores than those without. Prolonged amenorrhea is an added osteoporosis risk in WLWH.

Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial

ObjectiveNormal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low bone mineral density (BMD). Data are lacking regarding the impact of oestrogen administration on bone outcomes in OAA. Our objective was...

Bone accrual in oligo-amenorrheic athletes, eumenorrheic athletes and non-athletes.

Mechanical loading improves bone mineral density (BMD) and strength while decreasing fracture risk. Cross-sectional studies show that exercise advantage is lost in oligo-amenorrheic athletes (OA). Longitudinal studies examining the opposing effects of exercise and hypogonadism on bone are lacking in adolescents/young adults. Evaluate differences in bone accrual over 12 months in OA, eumenorrheic athletes (EA) and non-athletes (NA). We hypothesized that bone accrual would be lower in OA than EA and NA, with differences most pronounced at non-weight bearing trabecular sites. 27 OA, 29 EA, and 22 NA, 14-25 years old, completed 12-months of the prospective study. Athletes were weight-bearing endurance athletes. Subjects were assessed for areal BMD and bone mineral content (BMC) using DXA at the femoral neck, total hip, lumbar spine and whole body (WB). Failure load (a strength estimate) at the distal radius and tibia was assessed using microfinite element analysis of data obtained via high resolution peripheral quantitative computed tomography (HRpQCT). The primary analysis was a comparison of changes in areal BMD, BMC, and failure load across groups over 12-months at the respective sites. Groups did not differ for baseline age, height or BMI. Percent body fat was lower in both OA and EA compared to NA. OA attained menarche later than EA and NA. Over the follow-up period, OA gained 1.9 ± 2.7 kg of weight compared to 0.5 ± 2.4 kg and 0.8 ± 2.3 kg in EA and NA respectively (p = 0.09); 39% of OA resumed menses. Changes in BMD, BMD Z-scores, and tibial failure load over 12-months did not differ among groups. At follow up, EA had higher femoral neck, hip and WB BMD Z-scores than NA, and higher hip BMD Z-scores than OA (p < 0.05) after adjusting for covariates. At follow-up, radial failure load was lower in OA vs. NA, and tibial failure load lower in OA and NA vs. EA (p ≤ 0.04 for all). Change in weight and fat mass were associated with changes in BMD measures at multiple sites. Despite weight gain and menses recovery in many OA during follow-up, residual deficits persist without catch-up raising concerns for suboptimal peak bone mass acquisition.

Long-term Effect of Elagolix on Bone Mineral Density in Women with Endometriosis-Associated Pain [38G

INTRODUCTION: To evaluate the long-term effect of elagolix, an oral, non-peptide GnRH antagonist, on bone mineral density (BMD) in two 6-month (M) extension studies (Elaris EM-III and IV) of the pivotal, 6M, phase 3 studies (12M overall treatment with 150mg once daily [QD] or 200mg twice daily [BID]). METHODS: Women with moderate/severe endometriosis-associated pain and a baseline BMD Z-score &gt;-1.5 were randomized to receive elagolix in the pivotal studies and continued elagolix treatment in the extension studies (treated: Elaris EM-III, n=287; Elaris EM-IV, n=282). Total hip BMD was measured by dual energy X-ray absorptiometry and reviewed/evaluated by a blinded central reader. Baseline was before dosing in pivotal studies. RESULTS: After 6M of elagolix treatment in the pivotal studies, the proportion of women with a decrease in total hip BMD ≥8% ranged 0–1.1% across doses/studies; these women were not eligible for extension study. Following 12M treatment, the proportion of women with a total hip BMD decrease from baseline ≥8% was 1.8% (n=2) at 150mg QD and 0.9% (n=1) at 200mg BID in Elaris EM-III and 0% (n=0) at 150mg QD and 4.6% (n=5) at 200mg BID in Elaris EM-IV. For total hip, the mean BMD Z-score at extension-M6 was within the normal range of -2.0 to +2.0 across doses/studies; no women had a total hip BMD Z-score ≤-2. CONCLUSION: In women with endometriosis-associated pain, long-term elagolix treatment was associated with decreases in total hip BMD, while the mean total hip BMD Z-score was within the normal range and no women had a total hip BMD Z-score ≤-2.

Oxytocin and Its Relationship to Body Composition, Bone Mineral Density, and Hip Geometry Across the Weight Spectrum.

Oxytocin (OXT), an anorexigenic hypothalamic hormone anabolic to bone, may reflect energy availability. Basal serum OXT levels are lower in anorexia nervosa (AN, state of energy deficit) than healthy controls (HC) and negatively associated with spine bone mineral density (BMD). Reports are conflicting regarding OXT levels in overweight/obesity (OB, state of energy excess). Relationships between OXT and BMD in OB and hip geometry across the weight spectrum are unknown. To determine whether overnight serum OXT levels are (1) elevated in OB and (2) associated with body composition, BMD, and hip geometry across the weight spectrum. Cross-sectional. Clinical research center. Fifty-nine women, ages 18 to 45 years: amenorrheic AN (N = 16), eumenorrheic HC (N = 24), eumenorrheic OB (N = 19). Serum sampled every 20 minutes from 8 pm to 8 am and pooled for integrated overnight OXT levels. Body composition, BMD, and hip structural analysis measured by dual x-ray absorptiometry. OXT levels were lowest in AN, higher in HC, and highest in OB (P ≤ 0.02). There were positive associations between OXT and (1) body mass index (P = 0.0004); (2) total, visceral, and subcutaneous fat (P ≤ 0.0002); (3) spine and hip BMD Z-scores (P ≤ 0.01); and (4) favorable hip geometry, namely buckling ratio (P ≤ 0.05). In a subset analysis of HC and OB, relationships between OXT and body composition, but not bone parameters, remained significant. These data suggest OXT is a marker of energy availability and may be a mediator of bone density, structure, and strength. OXT pathways may provide targets for obesity and osteoporosis treatment.

Bone Accrual in Males with Autism Spectrum Disorder

To test the hypothesis that bone accrual over a 4-year period is reduced in boys with autism spectrum disorder (ASD) compared with typically developing controls. Twenty-five boys with ASD and 24 controls were assessed for bone outcomes. Fourteen boys with ASD and 11 controls were assessed both at baseline and after 4 years. The mean subject age was 11.0 ± 1.6 years at study initiation and 14.9 ± 1.6 years at follow-up. Bone mineral density (BMD) was measured at the spine, hip, and whole body using dual-energy X-ray absorptiometry and normalized for age, race, and sex (BMD z-scores). Height adjustments were performed as well. We assessed medical history, physical activity using questionnaires, vitamin D and calcium intake using food records, and serum calcium, phosphorus, 25(OH)-vitamin D, and pubertal hormone levels. Boys with ASD had lower spine, hip, and whole body BMD z-scores compared with controls. In those subjects assessed both at baseline and after 4 years, bone accrual rates did not differ between the 2 groups; however, spine and hip BMD z-scores remained lower in the boys with ASD than in controls at follow-up. Notably, the ASD group was less physically active at both time points. Although pubertal bone accrual was similar to that in controls, BMD in children with ASD remained low over a 4-year follow-up period, suggesting that low BMD is a consequence of prepubertal factors, such as low physical activity. Studies are needed to investigate the causes and consequences of decreased BMD, to assess BMD in females and adults with ASD, and to evaluate therapeutic interventions.

Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders.

Patients with autism spectrum disorder (ASD) are at increased risk for fracture, and peri-pubertal boys with ASD have lower bone mineral density (BMD) than controls. Data are lacking regarding BMD in older adolescents with ASD. We compared BMD using dual-energy X-ray absorptiometry in 9 adolescents/young adults with ASD against 9 typically developing matched controls. Patients with ASD and controls were excluded if they had other underlying conditions that may affect bone. Compared to controls, patients with ASD had (i) lower femoral neck and hip BMD Z-scores, and (ii) lower spine, femoral neck and hip height adjusted BMD Z-scores even after controlling for BMI. Understanding the underlying pathophysiology will be key to developing therapies to improve BMD and reduce fracture risk.

Regional fat depots and their relationship to bone density and microarchitecture in young oligo-amenorrheic athletes

ContextVarious fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking. MethodsWe used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18–25years). All athletes engaged in weight-bearing sports for ≥4h/week or ran ≥20miles/week. Main outcome measuresVAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture. ResultsGroups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p=0.048); L4 MAT was higher in OA than EA (p=0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r=−0.42, p=0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r=−0.44, p=0.01; r=−0.36, p=0.02), and vBMD of the radius and tibia (r=−0.49, p=0.002; r=−0.41, p=0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r≤−0.42, p≤0.01) and tibia (r≤−0.34, p≤0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model. ConclusionsVAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius.

The impact of osteoporosis on health-related quality of life in patients after liver transplantation - a pilot study.

IntroductionLiver transplantation (LT) is now a well-established procedure with 5-year survival rates over 70%, and one of its ultimate goals is the improvement of patient health-related quality of life (HRQOL). Osteoporosis remains a serious potential complication of LT, leading to fragility fractures, pain, and functional impairment.AimTo assess the degree of osteoporosis and the impact of fragility fractures on HRQOL in patients with chronic liver diseases treated with LT.Material and methodsTwenty-seven patients (14 female, 13 male) at a median period of 3.5 years post LT participated in the study. HRQOL was assessed by Short Form-36 and PBC-40 instruments. Bone mineral density (BMD) in the lumbar spine and hip neck were measured by dual-energy X-ray absorptiometry. Physical activity was assessed by questionnaire. Data on the duration of the liver disease, time from LT, and fragility fractures were also collected.ResultsAs many as 74.1% of the patients had reduced BMD (t-score < -1.0 SD) in the hip. Mean values of the spine and hip BMD z-scores were -1.1 and -0.9 SD, respectively. Time after LT, percentage of lean tissue, and physical activity were positively associated with BMD. The prevalence of fractures was 48%. We did not find significant differences in age, gender, body composition parameters, physical activity, BMD, and HRQOL scores between the subjects with and without fractures.ConclusionsWe found a high prevalence of fragility fractures and a decreased BMD in LT recipients. Patients with a history of fractures had similar HRQOL scores to those without fractures.

Higher bone turnover is related to spinal radiographic damage and low bone mineral density in ankylosing spondylitis patients with active disease: a cross-sectional analysis.

IntroductionAnkylosing spondylitis (AS) is characterized by excessive bone formation and bone loss. Our aim was to investigate the association of bone turnover markers (BTM) with spinal radiographic damage and bone mineral density (BMD) in AS patients with active disease.Methods201 consecutive AS outpatients of the Groningen Leeuwarden AS (GLAS) cohort were included. Serum markers of bone resorption (C-telopeptides of type-I collagen, sCTX) and bone formation (procollagen type-I N-terminal peptide, PINP; bone-specific alkaline phosphatase, BALP) were measured. Z-scores were used to correct for the normal influence that age and gender have on bone turnover. Radiographs were scored by two independent readers according to modified Stoke AS Spinal Score (mSASSS). The presence of complete bridging (ankylosis of at least two vertebrae) was considered as measure of more advanced radiographic damage. Low BMD was defined as lumbar spine and/or hip BMD Z-score ≤ −1.ResultsOf the 151 patients with complete data, 52 (34%) had ≥1 complete bridge, 49 (33%) had ≥1 syndesmophyte (non-bridging), and 50 (33%) had no syndesmophytes. 66 (44%) had low BMD. Patients with bridging had significantly higher sCTX and PINP Z-scores than patients without bridging (0.43 vs. −0.55 and 0.55 vs. 0.04, respectively). Patients with low BMD had significantly higher sCTX Z-score than patients with normal BMD (−0.08 vs. −0.61). After correcting for gender, symptom duration, and CRP, sCTX Z-score remained significantly related to the presence of low BMD alone (OR: 1.60), bridging alone (OR: 1.82), and bridging in combination with low BMD (OR: 2.26).ConclusionsThis cross-sectional study in AS patients with active and relatively long-standing disease demonstrated that higher serum levels of sCTX, and to a lesser extent PINP, are associated with the presence of complete bridging. sCTX was also associated with low BMD. Longitudinal studies are needed to confirm that serum levels of sCTX can serve as objective marker for bone-related outcome in AS.

Vascular calcification in patients undergoing kidney and simultaneous pancreas‐kidney transplantation

Vascular calcification (VC) is common in patients with chronic kidney disease (CKD) on dialysis, and an inverse relationship of VC to bone mineral density (BMD) has been reported. Because elderly patients are prone to atherosclerosis and BMD artefact, we examined the prevalence and epidemiology of VC in younger patients undergoing transplantation, and its relationship to BMD. Laboratory testing was performed immediately before kidney or simultaneous pancreas-kidney (SPK) transplantation. Within 4 weeks patients underwent BMD evaluation and lateral abdominal X-ray. Aortic calcification was scored using a validated 24-point scale. Of 650 consecutive patients X-rays were available for 531 (82%). Their median age was 41 years (16-71), 58% were male, dialysis vintage was 20 months (0-402) and 69% had kidney and 31% SPK transplants. VC scores were ≥1 in 47%, with the median score 6 (1-24) and was associated with age, dialysis vintage and presence of cardiovascular, cerebrovascular or peripheral vascular disease. In a multivariate analysis of patients with and without VC, those with VC were older and of longer dialysis vintage (OR 1.07 and 1.17 per 12 months respectively; P < 0.001 for both). In that analysis, VC was not significantly associated with gender, transplant type, presence of diabetes, current or former smoking or calcium or calcitriol therapy, and was not inversely related to hip, spine or forearm BMD Z-scores. VC is common in younger patients undergoing transplantation and, similar to older patients, is associated with age, dialysis vintage and cardiovascular pathology. However, in this younger patient group, there was no significant inverse association of VC to BMD.

Are serotonin metabolite levels related to bone mineral density in patients with neuroendocrine tumours?

Bone mineral density (BMD) is influenced by multiple factors. Recent studies have highlighted a possible relationship between serotonin and BMD. Patients with neuroendocrine tumours (NETs) frequently have elevated urinary 5-hydroxy-indoleacetic acid (5-HIAA) levels, a serotonin metabolite. Evaluation of the relationship between 5-HIAA and BMD in patients with NETs may provide insights into the relationship between serotonin and BMD. One-year audit of consecutive patients with NETs within two institutions. Relationships between urinary 5-HIAA and dual X-ray absorptiometry (DEXA)-scan-measured BMD were investigated by group comparisons, correlation and regression. Of 65 patients with NETs, 19 did not participate or were excluded. Of 46 subjects evaluated (48·9% males, 63·8 ± 10·5 years, BMI 26·6 ± 4·4 kg/m(2) ) with 32 gastrointestinal, 9 pancreatic, 3 pulmonary and 2 ovarian NETs, 72·3% had the carcinoid syndrome. Median interval from diagnosis was 4·0 years (IQR 2·0-6·0); 41·3% had osteoporosis and 32·6% osteopaenia (WHO definition). The group with a higher urinary 5-HIAA had a lower hip BMD (total T-score and Z-score), confirmed on individual analysis (Spearman's rank correlation -0·41, P = 0·004; -0·44, P = 0·002, respectively); urinary 5-HIAA was not found to be an independent predictor for BMD on multiple linear regression analysis. These data of patients with NETs with higher serotonin metabolites having a lower BMD at the hip in group and individual comparisons, warrants further evaluation. Urinary 5-HIAA measurement alone cannot be used to predict future BMD. A larger cohort with prospective design including fractures as a clinical outcome will aid these data in determining whether patients with NETs should be subject to targeted osteoporosis prevention.

SAT0251 Bridging Syndesmophytes and Low Bone Mineral Density are Associated with Higher Bone Turnover in Ankylosing Spondylitis Patients with Active Disease

BackgroundAnkylosing spondylitis (AS) is characterized by the combination of inflammation, bone formation, and bone loss. New bone formation can lead to the formation of syndesmophytes, ankylosis of the spine and...