Bone Mineral Density Z-score Research Articles

Effectiveness and safety of bisphosphonates therapy in secondary osteoporosis in children

IntroductionThere are few studies on effectiveness and safety of bisphosphonate therapy in secondary osteoporosis in children. The aim of this research was to analyse effectiveness and safety of bisphosphonates in secondary osteoporosis in children. Patients and methodsMulticentre retrospective study in patients younger than 18 suffering from secondary osteoporosis and who have received bisphosphonates. Clinical data were recorded. Bone mineral density (BMD) was assessed in terms of BMD Z-score in lumbar spine (ZBMDls) measured by dual-energy X-ray absorptiometry (DXA). Effectiveness was valued at changes in ZBMDls one and two years after the onset of bisphosphonates and at the decrese in the number of fractures a year. Adverse events reported were recorded. Descriptive and bivariant analysis was performed. Results32 patients were recruited. ZBMDls increased one year after the onset of treatment ((−2.46 ± 0.96) vs. (−1.54 ± 1.38); p < .001). Fractures a year dicreased significantly (1 (1–2) vs. 0 (0–0.61); p < .001). ZBMDls increase was higher in patients who were able to walk (1.88 ± 0.72 vs. 0.55 ± 0.82; p = .07) and correlated positively with body mass index (BMI)- for- age percentile (rho: 0.564; p < .001). The decrease in the number of fractures a year was higher in patients with lower initial fracture rate (rho: −0,47; p = .006) and with higher initial ZBMDls (rho: −0.47; p = .07). 10 adverse events were reported in 7 patients (22%), all of them intravenous bisphosphonates related. No association was found between adverse events and studied variables. ConclusionsBisphosphonates are effective in secondary osteoporosis in children. Response seems to be better in patients who are able to walk, well-nourished and in the early stages of the disease. Adverse events were frequent but mild.

Interpretation of Bone Mineral Density Z-Scores by Dual-Energy X-Ray Absorptiometry in Transgender and Gender Diverse Youth Prior to Gender-Affirming Medical Therapy

Interpretation of Bone Mineral Density Z-Scores by Dual-Energy X-Ray Absorptiometry in Transgender and Gender Diverse Youth Prior to Gender-Affirming Medical Therapy

Identification of a novel splicing mutation and genotype–phenotype correlations in rare PLS3-related childhood-onset osteoporosis

BackgroundX-linked early-onset osteoporosis, caused by mutations in plastin3 (PLS3), is an extremely rare disease characterized by low bone mineral density (BMD) and recurrent osteoporotic fractures. There is limited information on genetic and phenotypic spectrum, as well as genotype–phenotype correlations of the disease. Moreover, whether decreased PLS3 levels were also involved in osteoporosis among subjects without PLS3 pathogenic mutations remains unknown.MethodsWhole-exome sequencing and bidirectional Sanger sequencing were performed for screening and validation of pathogenic mutations. Serum biochemical parameters and clinical information of the subjects were retrospectively collected. ELISA and online datasets were utilized to investigate the association between PLS3 expression and BMD.ResultsWe identified a novel splicing mutation (c.892-2A > G) which led to the skipping of exon 9 in a family with X-linked early-onset osteoporosis. Scoliosis represents a potential new phenotype in the patients harboring PLS3 mutations, which may be corrected by brace treatment. Genotype–phenotype analysis reveals that there was no significant difference in BMD z-scores between different types of reported mutations including this study (p = 0.5). There is a marginally significant negative correlation between age and BMD z-score (p = 0.059, r = − 0.30). The conditions of osteoporosis in all patients were improved after bisphosphonates therapy, with mean BMD z-score increased from − 2.9 to − 0.57 (p < 0.0001). Serum PLS3 levels in adolescents and adults without PLS3 pathogenic mutations but representing osteoporosis were also evaluated, while no association was found between bone mineral density and PLS3 levels (p > 0.05).ConclusionsOur findings expanded the mutation and phenotype spectrum of the rare disease and highlights the importance of early diagnosis and early treatment with bisphosphonates. More reports of cases with PLS3 mutation and function studies of the gene are warranted to understand genotype–phenotype correlations.

Relationship of Pathogenic Mutations and Responses to Zoledronic Acid in a Cohort of Osteogenesis Imperfecta Children.

Osteogenesis imperfecta (OI) is a rare, heterogeneous, genetic disorder characterized by bone fragility and recurrent fractures. Bisphosphonates (BPs) are the most commonly used medications for OI, but their efficacy has great variability. We investigated the relationship of pathogenic gene mutations and responses to zoledronic acid (ZOL) in a large cohort of children with OI. Children with OI who received ZOL treatment were included and were followed up for at least 1 year. Bone mineral density (BMD) and serum levels of β-isomerized carboxy-telopeptide of type I collagen (β-CTX, bone resorption marker) were measured at baseline and during follow-up. Causative mutations of OI were identified using next-generation sequencing and Sanger sequencing. 201 children with OI were included. They had initiated ZOL treatment at a median age of 5 years, with mutations identified in 11 genes. After 3 years of treatment, the increase in femoral neck BMD Z-score in patients with OI with autosomal dominant (AD) inheritance was greater than that in patients with autosomal recessive or X-linked inheritance (non-AD) (4.5 ± 2.9 vs 2.0 ± 1.0, P < .001). Collagen structural defects were negatively correlated with the increase in femoral neck BMD Z-score. Patients with collagen structural defects had higher incidence of new fractures (35.1% vs 18.4%, relative risk 0.52, P = .044) and less decline in β-CTX level than those with collagen quantitative reduction. Increase in lumbar spine BMD and change in height Z-score was not associated with the genotype of children with OI. Patients with OI with non-AD inheritance or with pathogenic mutations leading to collagen structural defects may have relatively poor responses to ZOL treatment, which is possibly associated with their more severe phenotypes. New therapeutic agents are worth developing in these patients.

Childhood type 1 diabetes is associated with abnormal bone development.

ObjectiveTo describe bone mineral density (BMD), bone structure, and fracture prevalence in adolescents with type 1 diabetes (T1D) and explore their associations with glycemic control and microvascular complications.Research design and methodsCross sectional study of 64 adolescents (38 males) with T1D duration >10 years who underwent dual‐energy X‐ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), fracture survey, plantar fascia thickness, and microvascular complications assessment.ResultsMean age was 16.6 ± 2.1 years, diabetes duration 12.8 ± 2.2 years and HbA1c 8.9 ± 1.7% (74 mmol/mol). Fracture prevalence was 50%. DXA areal BMD (Z‐score) was reduced for femoral neck (−0.5 ± 1.3, p = 0.008) and arm (−0.4 ± 1.0, p < 0.001), while total areal BMD and lumbar spine BMD were normal. In pQCT (Z‐score), trabecular volumetric BMD (vBMD) was reduced for tibia (−0.4 ± 0.8, p < 0.001) and radius (−0.8 ± 1.4, p < 0.001) whereas cortical vBMD was increased at both sites (tibia: 0.5 ± 0.6, p < 0.001, radius: 0.7 ± 1.5, p < 0.001). Muscle cross‐sectional area (CSA) was reduced for upper (−0.6 ± 1.2, p < 0.001) and lower (−0.4 ± 0.7, p < 0.001) limbs. DXA total areal BMD was positively correlated with BMI (p < 0.01) and age at T1D diagnosis (p = 0.04). Lower radial bone CSA, total and lumbar spine BMD were associated with autonomic nerve dysfunction. HbA1c, diabetes duration, fracture history and other microvascular complications were not significantly associated with bone parameters.ConclusionsAdolescents with childhood‐onset T1D have site‐specific bone deficits in upper and lower limbs but normal total and lumbar spine BMD. T1D appears to have differential effects on trabecular and cortical bone compartments. Future longitudinal analysis is warranted to examine whether these changes translate in to increased fracture risk.

High Fetuin-A Levels in Children with Celiac Disease

Fetuin-A is a multifunctional non-collagen protein that plays a role in bone mineralization. Celiac disease is a chronic inflammatory disorder of the small intestine due to exposure to gluten. In this research, it was aimed to investigate levels of Fetuin-A and its relationship with bone mineral density in children with celiac disease. The study was conducted on 59 children with celiac and 29 healthy children. The celiac disease group was composed of three groups, newly diagnosed, gluten-free diet compliant and, non- gluten- free diet compliant patients. Serum Fetuin-A concentrations were measured by an enzyme-linked immuno- sorbent assay kit. Measurement of bone mineral density was performed a dual-energy x-ray absorptiometry. Serum Fetuin-A levels were 136.85 ± 38.09 μg/L and 112.95 ± 44.39 μg/L in the celiac disease and healthy control groups, respectively. There was a statistically significant difference between groups in levels of serum Fetuin-A (P < .05). A significant positive correlation was observed between serum Fetuin-A and bone mineral density Z-score in the celiac patients. Increased Fetuin-A levels and positive correlation between Fetuin-A and bone mineral density in children with celiac disease suggest that Fetuin-A may be a biomarker for celiac disease.

The relationship between metabolic syndrome and bone mineral density in adolescents: analysis of the National Health and Nutrition Examination Survey.

The purpose of this study was to observe the relationship between metabolic syndrome (MetS) and height (Ht) adjusted Z-scores for areal bone mineral density (aBMD) in adolescents. A retrospective study was conducted on the United States adolescents aged 12-17years. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011-2012, 2013-2014 and 2015-2016 cycles. Ht adjusted Z-scores for aBMD were calculated. A total of 969 adolescents (493 boys and 476 girls), aged 14.5±1.7years were enrolled in this study. After control for age, gender, race, 25-hydroxyvitamin D [25(OH)D], and lean body mass index (LBMI) Z-score, adolescents with MetS had significantly lower levels of total body (less head) aBMD Ht-Z-adjusted Z-score than adolescents with one, two components of MetS and without component of MetS (p<0.05) and significantly lower levels of lumbar spine aBMD Ht-Z-adjusted Z-score than adolescents with one component of MetS and without component of MetS (p<0.05). There were significantly negative associations between total body (less head) aBMD Ht-Z-adjusted Z-score and waist circumference (WC) (β=-0.027, p<0.001, R2=0.057) and homeostasis model assessment insulin resistance (HOMA-IR) (β=-0.225, p<0.001, R2=0.016). There were significantly negative associations between lumbar spine aBMD Ht-Z-adjusted Z-score and WC (β=-0.039, p<0.001, R2=0.058) and HOMA-IR (β=-0.251, p<0.001, R2=0.008). The present study demonstrates that MetS may have a negative effect on bone mineral density in adolescents. Abdominal obesity and insulin resistance play a major role on the decline of aBMD in adolescents.

Linoleic Acid Reduces Oxidative Phosphorylation and Impairs Early Differentiation of MC3T3-E1 Osteoblast Precursor Cells

ObjectivesUntargeted metabolomics analyses by our group have shown that plasma linoleic acid (LA) was inversely associated with bone mineral density Z-score and that bone formation indices were associated with energy-generating metabolic pathways, including fatty acid b-oxidation, in adult cohorts. Here, we examined the effect of increasing LA concentrations on osteoblast precursor cell bioenergetics and osteoblast differentiation to determine whether high LA is detrimental to bone formation. MethodsWe treated MC3T3-E1 pre-osteoblastic cells with 0 μM (control), 1 μM, and 50 μM LA cultured in osteogenic differentiation media supplemented with 50 μM L-ascorbic acid and 2 mM β-glycerophosphate. To assess the effect of LA on early commitment/differentiation, cells were stained for alkaline phosphatase activity and late differentiation using Alizarin Red S staining for mineral deposition, at 7 and 18 days, respectively. To assess cellular bioenergetics, real-time ATP production rates in LA treated (1 or 50 μM) and control MC3T3-E1 cells were measured using an extracellular flux analyzer after 24 hours (normalized for total protein content). Differences in bioenergetic values were determined using one-way ANOVA or Kruskal-Wallis test with Tukey’s HSD or Dunn’s post hoc tests. ResultsWhile LA had no effect on late differentiation/mineralizing activity of MC3T3 cells, LA dose-dependently decreased commitment/early differentiation. LA also significantly altered the bioenergetic profile of MC3T3-E1 cells by decreasing basal oxygen consumption rate (P < 0.001), as well as mitochondrial and total ATP production rate (P < 0.05 and P < 0.001, respectively). There were no significant changes in glycolytic ATP production rate. ConclusionsOsteoblast differentiation is a highly bioenergetic process, and this study suggests excess LA may impair ATP production from oxidative phosphorylation. This, in turn, may impede commitment and early differentiation of osteoblasts. Our study supports further clinical and translational investigation into the role of LA and energy metabolism in osteoblast function, as well as bone formation. Funding SourcesNational Institutes of Health.

Total n-6 Polyunsaturated Fatty Acid and Linoleic Acid Dietary Intakes Are Associated With Lower Serum Osteocalcin Among Postmenopausal Women

ObjectivesOur research group has recently shown that plasma linoleic acid (LA), an essential n-6 polyunsaturated fatty acid (PUFA), was inversely associated with whole body bone mineral density (BMD) Z-score in a general US adult population. We aimed to determine whether dietary LA, arachidonic acid (AA) or total n-6 intake are likewise associated with serum bone turnover markers (BTMs) and BMD at sites prone to fracture, including total hip, lumbar spine, and femoral neck, among postmenopausal women without osteoporosis. MethodsThis was a cross-sectional study of healthy women (N = 34; 50–65 years) with onset of menopause < 5 years. Fasting serum samples were obtained, and BMD indexes were measured by dual X-ray absorptiometry (DXA) in the same visit. BMD values were converted to T-scores. Three-day food records were collected, and calorie-adjusted nutrient intakes calculated using Nutrition Data System for Research software. Serum concentrations of osteocalcin (OC, a bone formation biomarker) and C-terminal telopeptides of Type I collagen (CTX, a bone resorption biomarker) were measured by ELISA. Relationships between LA and each BMD T-score and serum BTM were assessed using linear regression adjusting for age, race, and body mass index. ResultsTotal n-6 PUFA and LA intakes were not significantly associated with any BMD T-scores. AA intake was positively associated with lumbar spine BMD T-score [β = 10.4, (95% CI: 0.3, 20.5), P < 0.04]. For serum BTMs, total n-6 PUFA and LA intakes were inversely associated with serum osteocalcin [β = –6.8, 95% CI: (–13.2, –0.5) and β = –6.8, 95% CI: (–13.1, –0.5) respectively, both P < 0.05] but not significantly associated with serum CTX. AA intake was not significantly associated with either BTM. ConclusionsDietary intake of total n-6 PUFAs and LA were inversely associated serum OC, while AA intake was positively associated with lumbar spine BMD. Cellular mechanistic and intervention studies in clinical populations are needed to confirm effects of total n-6 PUFA, LA, and AA intake on bone formation and BMD over time. Funding SourcesNational Institutes of Health, John and Mary Brock Discovery Fund.

Vitamin D Supplementation and Muscle Strength and Bone Health Outcomes: A Phase 3 Randomized Trial in 8,851 Schoolchildren

ObjectivesTo determine the effects of vitamin D supplementation on muscle strength and bone health in vitamin D-deficient schoolchildren. MethodsWe performed a phase 3 randomized placebo-controlled clinical trial in Ulaanbaatar, Mongolia, to determine whether weekly oral supplementation with 14,000 IU vitamin D3, administered for 3 years in 8,851 schoolchildren aged 6 to 13 years. We evaluated effects of the intervention on bone mineral density (BMD) (n = 1,465), physical fitness (n = 615), long jump (n = 8,850), grip strength (n = 8,850) and incidence of fracture (n = 8,850). Analyses were conducted for all efficacy outcomes to determine whether the effect of the intervention varied according to baseline 25-hydroxyvitamin D levels and calcium intake. ResultsOf the 8,851 randomized participants, 95.6% had vitamin D deficiency (25[OH]D < 20 ng/mL) at baseline, and 91.7% completed the study. Mean end-study 25(OH)D levels were 29.8 vs. 9.7 ng/mL in children randomized to intervention vs. placebo (p < 0.001). Vitamin D supplementation did not reduce the incident fracture (P = 0.65), mean radial BMD z-score (P = 0.14), mean maximal oxygen consumption during a 20 meter shuttle run (VO2max, P = 0.22), mean grip strength (p = 0.77) and mean long jump distance (p = 0.23). Effects of the intervention did not differ according to baseline 25-hydroxyvitamin D levels (<10 ng/mL vs. ≥10 ng/mL) for any efficacy outcome studied in subset population. ConclusionsA weekly oral dose of 14,000 IU (3.5 mg) vitamin D3, administered for 3 years, was safe and effective in elevating 25-hydroxyvitamin D levels into the high physiological range in vitamin D-deficient schoolchildren, but it did not affect any efficacy outcome in muscle strength and bone health. Funding SourcesNational Institutes of Health, 1R01HL122624-01.

Relation between the insulin lowering rate and changes in bone mineral density: Analysis among subtypes of type 1 diabetes mellitus.

Aims/IntroductionThe bone mineral density in patients with type 1 diabetes mellitus is reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. This study aimed to clarify the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute‐onset (AO), and fulminant (F).MethodsThis was a retrospective, single‐center, cross‐sectional study conducted on 98 adult type 1 diabetes mellitus patients. The main outcome included the bone mineral density Z‐score (BMD‐Z) measured at the lumbar spine and femoral neck.ResultsThe lumbar spine BMD‐Z was lower in the acute‐onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD‐Z tended to be higher in the slowly progressive than in the acute‐onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD‐Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C‐peptide immunoreactivity (CPR). When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute‐onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD‐Z differed between the acute‐onset and slowly progressive only in the second tertiles (both P < 0.01), with a similar tendency between the fulminant and slowly progressive subtypes.ConclusionsAmong the type 1 diabetes mellitus subtypes, bone mineral density undergoes time‐dependent changes, which reveals that the bone mineral density decline follows the impaired insulin secretion. These results provide novel insights into the association between the low insulin exposure duration and bone mineral density.

Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease

Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42Caserum ratio and parathyroid hormone. The44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

Effects of Hormone Replacement Therapy on Low Bone Mineral Density in Adolescents and Young Women with Hypogonadism: Comparison of Oral and Transdermal 17 Beta-Estradiol Administration

To evaluate the effects of physiological dose 17 beta-estradiol (E2) replacement on low bone mineral density (BMD) and compare the results of oral and transdermal (TD) E2 administration in adolescents and young women with hypogonadism DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed the medical records of patients aged 15 to 24 years who were diagnosed with hypogonadism, who had begun receiving oral or TD E2 replacement, and whose initial dual-energy X-ray absorptiometry scan detected a lumbar spine BMD Z-score of -1 or lower between 2014 and 2018. The patients were divided into 2 groups according to the E2 route of administration as those who received 2 mg orally (Group 1) and 0.1 mg TD (Group 2). None MAIN OUTCOME MEASURE: BMD scans of the patients at baseline and repeated within 2 years after E2 replacement RESULTS: In total, 43 patients who met the inclusion criteria were included in the study. Two groups did not differ for BMD scores at baseline. A significant improvement in BMD was observed with physiological dose E2 replacement in both groups. Mean BMD Z-score increased by +0.7 (95% CI, 0.47-0.93) in response to TD E2 administration, compared with +0.41 (95% CI, 0.25-0.58) during oral E2 replacement (P=.037). We conclude that physiological dose E2 replacement, even within a short period of 2 years, has a significant beneficial effect on bone mass acquisition on the lumbar spine. Our study also demonstrates the possible superiority of TD E2 replacement over the oral route in increasing lumbar spine BMD.

Reduced bone mineral density in adolescents with Duchenne Muscular Dystrophy (DMD) and scoliosis

SummaryDuchenne muscular dystrophy is a progressive disease usually associated with loss of ambulation and progressive scoliosis. Immobilisation and glucocorticoid treatment are predisposing factors for reduced bone mineral density (BMD). Analysis of quantitative computed tomography revealed low BMD in thoracic and lumbar vertebrae in comparison to age- and sex-matched healthy controls.IntroductionEvaluation of vertebral bone mineral density (BMD) in Duchenne Muscular Dystrophy (DMD) adolescents with untreated advanced scoliosis and comparison with the BMD values of healthy age-matched controls, based on quantitative computer tomography.MethodsThirty-seven DMD adolescents (age 15.6 ± 2.5 years) with spinal deformity were evaluated clinically and radiologically prior to definite spinal fusion and compared to 31 male and age-matched healthy individuals (age 15.7 ± 2.3 years). Data related to previous medical treatment, physiotherapy and ambulatory status was also analysed. Scoliotic curves were measured on plain sitting radiographs of the spine. The BMD Z-scores of the thoracic and lumbar vertebrae were calculated with QCTpro® (Mindways Software Inc., USA), based on data sets of preoperative, phantom pre-calibrated spinal computed tomography scans.ResultsA statistically significant lower BMD could be found in DMD adolescents, when compared to healthy controls, showing an average value for the lumbar spine of 80.5 ± 30.5 mg/cm3. Z-scores deteriorated from the upper thoracic towards the lower lumbar vertebrae. All but the uppermost thoracic vertebrae had reduced BMD values, with the thoracolumbar and lumbar region demonstrating the lowest BMD. No significant correlation was observed between BMD and the severity of the scoliotic curve, previous glucocorticoid treatment, cardiovascular impairment, vitamin D supplementation, non-invasive ventilation or physiotherapy.ConclusionDMD adolescents with scoliosis have strongly reduced BMD Z-scores, especially in the lumbar spine in comparison to healthy controls. These findings support the implementation of a standardised screening and treatment protocol.Level of evidence/clinical relevance: therapeutic level III

The Influence of Low Energy Availability on Bone Mineral Density and Trabecular Bone Microarchitecture of Pubescent Female Athletes: A Preliminary Study.

The influence of low energy availability (LEA) on bone mineral density (BMD) and trabecular bone microarchitecture in pubescent female athletes is unclear. This study aimed to investigate the influence of LEA on BMD and trabecular bone microarchitecture in 21 pubescent female athletes (age, 12–15 years; 11 track and field athletes, 10 gymnasts). We used two indices to assess LEA: energy availability and the percent of ideal body weight. Dual-energy X-ray absorptiometry was used to obtain total body less head, lumbar spine BMD Z-scores, and lumbar trabecular bone scores (TBS). Pearson’s or Spearman’s correlation coefficients were used to assess the relationship among EA, percent of ideal body weight, and bone parameters. The threshold for statistical significance was set at p < 0.05. The percent of ideal body weight was significantly correlated with the BMD Z-scores of the total body less head (r = 0.61; p < 0.01), lumbar spine (r = 0.55; p < 0.01), and lumbar TBS (r = 0.47; p = 0.03). However, energy availability was not correlated with bone parameters. These findings suggest that screening for low ideal body weight may be a useful predictor of low BMD and insufficient trabecular bone microarchitecture in pubescent female athletes.

MO038: Mineral bone density assessment in patients affected by cystinuria

Abstract BACKGROUND AND AIMS Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine and other dibasic amino acids that leads to cystine renal calculi. Although being a rare condition, cystinuria is the most frequent monogenic cause of nephrolithiasis accounting for 1% of kidney stones in adults and 8% in children with an average prevalence of 1 in 7000 births. Up to date, clinical features of cystinuria are believed to be attributable only to nephrolithiasis although cystinuric patients may present other comorbidities (chronic kidney disease, progression toward end-stage kidney disease and hypertension). All these features may be partially explained by recurrent nephrolithiasis. There are currently no data on bone features of patients with cystinuria. Data on a murine model demonstrated the presence of reduced bone mineral density irrespective of the presence or absence of uremia, suggesting bone metabolic abnormalities in cystinuria even in the absence of reduced glomerular filtration rate (GFR). Our aim is to characterize bone mineral density (BMD) in patients affected by cystinuria. METHOD The present study included 13 patients affected by cystinuria followed at the Rare Kidney Diseases outpatient clinic of our Institution. All eligible patients were more than 18 years of age with an estimated GFR ≥15 mL/min/1.73 m2 and provided written informed consent. Patients who did not sign informed consent, pregnant women, patients undergoing chronic hemodialysis or with a previous kidney transplant were excluded. History and laboratory data were collected during scheduled outpatient visits from September 2021 to December 2021, and all patients underwent a dual-energy X-ray absorptiometry (DEXA). One sample t-tests were used to assess whether BMD Z-scores were significantly different from 0. RESULTS Patients’ characteristics are summarized in Table 1. Of the enrolled patients, six (46%) were female and four of them (67%) were in menopause, four (31%) had active nephrolithiasis described as at least two episodes in the last 3 months, and two (15%) had a self-reported diagnosis of osteoporosis. Moreover, six patients (46%) had a positive history for bone fractures that were all self-reported as traumatic. Femoral Z-scores were significantly lower than 0 overall (P = 0.015) and across femoral sites, whereas lumbar Z-scores, although low on average, did not meet statistical significance (Figure 1). Interestingly, reduced BMD was very prevalent, with 10 patients (77%) showing osteopenia and 3 (23%) showing osteoporosis. CONCLUSION Our data show a high prevalence of osteopenia and osteoporosis in cystinuric patients, especially when considering that our population was rather young and with a normal or moderately impaired kidney function. Of further interest appears also the differential distribution of decreased BMD that seems to be affecting the femur rather than the lumbar spine. To our knowledge, these are the first data assessing the prevalence and the characteristics of BMD disorder in cystinuric patients.

MO552: Self-Administered Exercise and Bone Mineral Density in Patients With Chronic Kidney Disease: A Substudy of Renexc—A Randomized Controlled Trial

Abstract BACKGROUND AND AIMS The aim of the study was to evaluate the effects of 12 months self-administered exercise training on bone mineral density (BMD) in non-dialysis-dependent patients with chronic kidney disease stages 3–5. METHOD In this single-centre, randomized controlled trial, 151 patients were allotted 60 minutes of endurance training in combination with 90 minutes of either balance or strength training. The exercise was prescribed and monitored by a physiotherapist and performed at home or a gym. Total body-, hip- and lumbar BMD (g/m2), T-score and Z-score were measured at baseline (T0) and after 12 months (T12) using dual-energy X-ray absorptiometry (DEXA). A total of 112 patients completed the study. Of these, five patients were excluded from analysis because they missed either the T0 or T12 DEXA evaluation. To evaluate between-group changes after the study period delta BMD, delta T-score and delta Z-score values (T12 value–T0 value) were calculated. These results were also used to define progressors and non-progressors. Statistical analyses were performed using SPSS for Windows 24. Statistical significance was assessed using Student's t-test, paired-sample t-test, Mann–Whitney or Wilcoxon matched-pairs signed-rank tests depending on normality of data distribution. The two-tailed chi-squared test was used to compare categorical variables. Values are given as mean ± SD or median (min-max). A P-value &amp;lt; 0.05 was accepted as the level of significance. RESULTS A total of 107 patients [69 men, 38 women; age 66 ± 13.5 years, measured glomerular filtration rate (GFR) 22 ± 8 mL/min/1.73 m2] were analysed. There were 50 patients (34 men, 16 women) in the strength group and 57 (35 men, 22 women) in the balance group. After 12 months of training the whole group showed a statistically significant decrease in hip BMD [0.886 (0.479–1.922) T0 versus 0.873 (0.521–2.045) T12, P = 0.002], hip T score [−1.177 ± 1.419 T0 versus − 1.4 (−4.0 to 6.6) T12, P = 0.049] and total body BMD (1.156 ± 0.508 T0 versus 1.149 ± 0.164 T12, P = 0.032). When data were analysed separately within each group, the strength group showed a decrease in total body BMD (1.152 ± 0.151 T0 versus 1.141 ± 0.153 T12, P = 0.001). Changes in total body T-score and Z-score did not reach the level of significance (T-score − 0.392 ± 1.56 T0 versus − 0.484 ± 1.56 T12, P = 0.138; Z-score 0.07 ± 1.19 T0 versus − 0.012 ± 1.21 T12, P = 0.052). The balance group showed a statistically significant increase after 12 months training in total body T-score (−0.312 ± 1.659 T0 and − 0.196 ± 1.707 T12, P = 0.035) and total body Z-score [0.05 ± 1.626 T0 and 0.4 (−5.1 to 6.8) T12, P = 0.003] but not in total body BMD [1.16 ± 0.151 T0 versus 1.123 (0.668 to 1.818) T12, P = 0.135]. Delta total body T-score was negative in the strength group [−0.10 (−1.0 to 2.1) and unchanged in the balance group 0.00 (−0.60 to 1.00), showing a significant between-group difference (P = 0.005)]. Delta total body Z-score was negative in the strength group (−0.092 ± 0.430) and positive in the balance group (0.1158 ± 0.403) showing a significant between-group difference (P = 0.001). Moreover, the proportion of progressors was higher in the strength group as shown by the delta total body T-score (60%) strength versus (40%) balance group (P = 0.006) and delta total body Z-score (61%) and (40%) respectively (P = 0.029). CONCLUSION Balance—in combination with endurance training seemed to be superior to strength—in combination with endurance training in preserving and even improving bone health. The 12 months of balance training resulted in an increase in total body T-score and Z-score, respectively. The strength group showed a decrease in total body BMD after 12 months of training. Moreover, when comparing the delta values there were significant between-group effects with the balance group showing an unchanged T-score in comparison with the strength group's decreased T-score and a positive Z score in comparison with the strength group's negative value. Finally, a greater proportion of participants in the strength group were classified as progressors with a deterioration of bone health.

Prevalence and risk factors of fractures in transfusion dependent thalassemia - A Hong Kong Chinese population cohort.

ObjectiveTo delineate the prevalence and associated risk factors of low BMD, osteoporosis/bone fragility and fracture in transfusion‐dependent thalassemia (TDT) in the Chinese population in Hong Kong.Design, Patients and MeasurementsA retrospective cohort study design was employed. Patients of TDT who had serial Hologic dual‐energy X‐ray absorptiometry (DXA) from 2010 to 2016 and received regular transfusion for at least 5 years were recruited. Clinical and biochemical data, from 5 years before the first DXA scan, were retrieved from the electronic record system of the Hospital Authority, till 30 June 2020. Low bone mineral density and osteoporosis/bone fragility are defined by the ISCD 2019 position guidelines.ResultsSeventy‐seven patients were included in the analysis. The fracture prevalence of TDT among the Chinese population in Hong Kong was 15.58%. Up to 55.84% of patients had low bone mineral density, and 5.19% patients had osteoporosis/bone fragility state. The median age at first fracture was 31.73 years (range 24.06–44.18 years). In the regression analysis, a higher log(10) transformation of average ferritin levels over 5 years before the first DXA scan was significantly associated with fracture occurrence regardless of bisphosphonate treatment (OR 310.73, 95% CI 3.99–24183.89, p = .010). Mean average ferritin level over 5 years was 6695.5 ± 2365.7 pmol/L (fracture group) versus 4350.7 ± 3103.2 pmol/L (non‐fracture group), p = .016. Hip and spine BMD Z‐score did not have statistically significant association with fracture occurrence.ConclusionIron overloading plays an important role in adverse bone health in TDT. Dual X‐ray densitometry is insufficient in predicting fracture risk.

P131 Adult coeliac disease and bone mineral density at the femoral neck, total hip and lumbar spine: an age- and sex-matched case-control study

Abstract Background/Aims Coeliac disease (CD) is characterised by intestinal villous atrophy causing malabsorption. Decreased bone mineral density (BMD) has been reported in CD. To the best of our knowledge, no published paper has documented BMD comparisons in detail at different sites. We aim to determine the prevalence of osteoporosis and BMD values at multiple locations in a group of adult CD patients, and compare them to those of age and sex matched controls. Methods We analysed data of adult patients referred for BMD estimation at a district scanner from 2004 to 2018. Dual-energy x-ray absorptiometry was used for all subjects. Patients diagnosed with CD (cases) were age- and sex-matched with subjects referred with no reason for scanning (controls). Additional FRAX(TM) risk factors for osteoporosis were recorded. Comparison was made using chi-squared for categorical values, student's T test for continuous variables, then a univariate followed by a multivariate stepwise logistic model, adjusting for height, weight and body mass index (BMI), were fitted. Results 645 (474 female) patients in the coeliac group were matched with 645 (474 female) controls. There was no significant difference in the mean age (years) at scan: cases 56.24 (SD 14.79) vs controls 56.24 (SD 14.80), p-value 1.00. The coeliac group had a significantly higher proportion of osteoporotic (T-score ≤-2.5 SD) patients at all locations compared to the control group. Cases had significantly lower mean BMD (gcm-2) and mean Z-scores at all locations than the controls. In the multivariate stepwise model, adjusted for height, weight and BMI, only the total hip, lumbar spine and their sub-sites revealed significant associations between having CD and a BMD (gcm-2) in the lowest tertile for the whole cohort. Key results are summarised in Table 1. Conclusion We confirmed that adult CD patients have higher prevalence of osteoporosis and lower BMD values compared to controls. Bone impairment was pronounced at the L1 and L2 vertebrae; least pronounced at the femoral neck. This might be due to CD preferentially damaging trabecular bone, which is predominant in the lumbar spine than femoral neck. Disclosure P. Shtarbanov: None. M. Bukhari: None.

Evaluation of bone mineral density (BMD) and the effect of type of factor replacement therapy on BMD in children with hemophilia: A single-center observational study

BackgroundThe higher life expectancy in patients with hemophilia (PWH) due to better care has increased the incidence of age-related complications such as osteoporosis. This study was conducted to assess the bone mineral density (BMD) and its correlation with determinants of hemophilic arthropathy and to evaluate the effect of type of factor replacement therapy on BMD in Indian hemophilic children. MethodsThis study was conducted on 39 hemophilic children and 40 healthy controls. Total range-of-motion (ROM) score was calculated for major affected joints and BMD was measured by dual-energy x-ray absorptiometry at baseline and repeated at follow-up after 6 months period during which all patients received either prophylaxis or on-demand therapy. ResultsBMD and BMD Z-scores were significantly reduced in hemophiliacs as compared to controls (p < 0.05). The prevalence of low BMD in hemophiliacs ranged from 30.8 to 41% at various sites. A significant correlation was found between BMD Z-score and episodes of joint bleed, number of target joints, and total joint ROM score (p < 0.05). BMD Z-score showed a significant difference between the prophylaxis group and on-demand therapy group at baseline, and a significant increase in BMD Z-score was observed among patients in prophylaxis group at follow-up after 6 months compared to baseline (p < 0.05) but not among patients in on-demand therapy group. ConclusionsHemophilic children showed reduced BMD that correlated with hemophilic arthropathy. Prophylaxis, as compared to on-demand therapy, markedly decreased hemarthrosis and consequent immobilization, and thereby retarded the progression of bone mineral loss and improved BMD in these patients.