Attainment Of Peak Bone Mass Research Articles

Between a Rock and a Short Place-The Impact of Nephrolithiasis on Skeletal Growth and Development Across the Lifespan.

The impact of nephrolithiasis on skeletal growth and bone health across the life span of kidney stone formers is reviewed. Bone disease is an early event among kidney stone formers (SF), with distinct phenotypes according to each age, sex, menopausal status, dietary, hormonal and genetic factors. Nephrolithiasis-associated bone disorder is characterized by reduced bone mineral density (BMD) and histologically discloses low bone formation, high bone resorption and abnormal mineralization. Although hypercalciuria has been presumed to be pathogenic for bone loss in SF, the association of BMD with urinary calcium is not uniform in all studies. Hypocitraturia, metabolic disturbances, cytokines and receptors, growth factors and acid-base status may all influence skeletal outcomes. The potential link of bone disease with vascular calcification and cardiovascular disease among SF is discussed. The unique vulnerability of the younger skeleton to the effects of nephrolithiasis on attainment of peak bone mass and strength is highlighted and the association of bone loss with kidney stone formation early in life indicate the opportunity for intervention to reduce the risk of future bone fractures.

Sex-specific trisomic Dyrk1a-related skeletal phenotypes during development in a Down syndrome model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or trisomy 21 and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to those in typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30, when there were persistent trabecular and cortical deficits and Dyrk1a was trending toward overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with trisomy 21.

Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits and Dyrk1a was trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21.

Bone health screening practices with dual-energy X-ray absorptiometry and prediction of abnormal results in pediatric inflammatory bowel disease.

Pediatric patients diagnosed with inflammatory bowel disease (IBD) are at risk of suboptimal peak bone mass attainment. This study aimed to understand rates of bone health screening adherence, describe factors associated with dual-energy X-ray absorptiometry (DXA) acquisition, and identify factors associated with abnormal DXA. We performed a retrospective cohort study of pediatric IBD patients over a 10-year time frame. We included IBD patients (2-20 years of age) enrolled in ImproveCareNow and excluded patients with primary metabolic bone disease. Time-to-event methods and multivariable logistic regression were employed to identify factors associated with DXA acquisition and abnormal DXA. In 676 patients, 464 (68.63%) pediatric patients with IBD had a risk factor for low bone mineral density (BMD); 137 (29.53%) underwent an initial DXA scan. Quiescent disease was significantly associated with a reduced likelihood of DXA (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.24-0.97), while weight z-score <-2 was significantly associated with DXA performance (HR: 2.07; 95% CI: 1.08-3.98). Abnormal DXA results (BMD z-score ≤-1) occurred in 59 (35.54%) individuals. After adjusting for visit diagnosis, delayed puberty, severe disease course, 6 months or greater of steroid exposure, and history of fracture, BMI z-score <-1 (odds ratio: 5.45; 95% CI: 2.41-12.33) was associated with abnormal DXA. DXA screening occurred in less than one-third of eligible pediatric IBD patients. Compliance was more common in patients with a weight z-score <-2 and less common in those with quiescent disease. BMI strongly predicted abnormal DXA results when adjusting for risk factors for abnormal BMD.

Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

OR13-01 Type 1 Diabetes Is Associated With Differential Skeletal Effects At The Onset Of Peak Bone Accrual

Abstract Disclosure: A.V. Brossfield: None. K.M. Williams: None. A.B. Sopher: None. D.J. McMahon: None. J. Fernando: None. S. Agarwal: None. M.R. Rubin: None. Objective: Type 1 diabetes (T1D) often develops prior to attainment of peak bone mass, yet few data exist regarding bone accretion in the peri-pubertal period. We hypothesized that T1D have disrupted bone architecture at the onset of peak bone mass accrual in association with hyperglycemia and advanced glycation endproduct (AGE) accumulation. Methods: We enrolled T1D and controls at onset of peak bone accretion (Tanner: girls 2/3, boys 3/4) and assessed aBMD by DXA and volumetric BMD (vBMD), microarchitecture, and bone strength by high resolution peripheral quantitative computed tomography (HRpQCT) with finite element analysis (µFE) at the distal (4%) and proximal (30%) radius and tibia. We assessed time in hyperglycemia (&amp;gt;180 mg/dL) by continuous glucose monitoring and AGE accumulation by skin autofluorescence (SAF). Results: T1D (n=29, age 12.5 ± 0.3 [SE] yr, 79% male, 68% white) vs controls (n=31, 12.2 ± 0.3 yr, 55% male, 68% white) had higher BMI (21.3 ± 1 vs 18.4 ± 0.5 kg/m2; p=0.04), fasting glucose (168.5 ± 9 vs 88.4 ± 2 mg/dL; p&amp;lt;0.0001) and HbA1c (8.4 ± 0.8 vs 5.0 ± 0.2%; p=0.05) with a trend toward higher bone age (13.5 ± 0.3 vs 12.6 ± 0.3 yr, p=0.07) and lower 25OHD (24.0 ± 1 vs 34.8 ± 3 ng/mL, p=0.08). After multivariate adjustment (sex, bone age, height and weight), DXA showed decreased bone area in T1D at the total, sub-total, leg, rib and ultradistal radius, and decreased bone mineral content at the rib, leg and trochanter (ranging from -4.1% to -13.5%, all p &amp;lt;0.05). Multivariate adjusted HRpQCT data showed decreased trabecular area in T1D at the distal radius (169.9 ± 8 vs 201.2 ± 8 mm2; p=0.007) and tibia (578 ± 17 vs 631 ± 17 mm2; p=0.04) and decreased cortical perimeter at the distal radius (56.0 ± 1 vs 60.1 ± 1 mm2; p=0.009). However, T1D had increased cortical vBMD at the distal (698.2 ± 8 vs 663.5 ± 8 mg HA/cm3; p=0.004) and proximal radius (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and tibia (998 ± 6 vs 977 ± 6 mg HA/cm3; p=0.02) and increased cortical thickness at the distal radius (0.74 ± 0.03 vs 0.64 ± 0.03 mm; p=0.03). There was no difference in bone strength by µFE. Within T1D, lower trabecular area at the distal radius was associated with higher SAF (β -69.26 ± 30 mm2; p=0.04) while higher cortical vBMD at the distal tibia was associated with higher time in hyperglycemia (β 0.633 ± 0.3 mg HA/cm3; p=0.03). Conclusion: T1D at the onset of peak bone accrual have decreased bone area and mineral content by DXA. They also have decreased trabecular area but increased cortical vBMD by HRpQCT, in association with AGE accumulation and hyperglycemia. We speculate that reduced bone turnover with hyperglycemia might lead to reduced area at more metabolically active trabecular sites but is compensated for by excess mineral accumulation at less active cortical sites, with overall maintenance of bone strength. Follow up will elucidate progression of these alterations during the growth spurt. Presentation: Friday, June 16, 2023

Phlpp1 Expression in Osteoblasts Plays a Modest Role in Bone Homeostasis.

Prior work demonstrated that Phlpp1 deficiency alters limb length and bone mass, but the cell types involved and requirement of Phlpp1 for this effect were unclear. To understand the function of Phlpp1 within bone-forming osteoblasts, we crossed Phlpp1 floxed mice with mice harboring type 1 collagen (Col1a12.3kb)-Cre. Mineralization of bone marrow stromal cell cultures derived from Phlpp1 cKOCol1a1 was unchanged, but levels of inflammatory genes (eg, Ifng, Il6, Ccl8) and receptor activator of NF-κB ligand/osteoprotegerin (RANKL/OPG) ratios were enhanced by either Phlpp1 ablation or chemical inhibition. Micro-computed tomography of the distal femur and L5 vertebral body of 12-week-old mice revealed no alteration in bone volume per total volume, but compromised femoral bone microarchitecture within Phlpp1 cKOCol1a1 conditional knockout females. Bone histomorphometry of the proximal tibia documented no changes in osteoblast or osteoclast number per bone surface but slight reductions in osteoclast surface per bone surface. Overall, our data show that deletion of Phlpp1 in type 1 collagen-expressing cells does not significantly alter attainment of peak bone mass of either males or females, but may enhance inflammatory gene expression and the ratio of RANKL/OPG. Future studies examining the role of Phlpp1 within models of advanced age, inflammation, or osteocytes, as well as functional redundancy with the related Phlpp2 isoform are warranted. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Endocrine Health and Health Care Disparities in the Pediatric and Sexual and Gender Minority Populations: An Endocrine Society Scientific Statement.

Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.

Dietary intake of pistachios or mixed nuts results in higher systemic antioxidant capacity with minimal effects on bone in adolescent male rats.

Nutrition is a key determinant of bone health and attainment of peak bone mass. Excess oxidative stress induces bone loss while increasing antioxidant capacity promotes protective effects on bone. Nuts are rich in antioxidants; therefore, we tested the hypothesis that compared to a control diet high in fat (40 % energy) and cholesterol, diets containing isocaloric amounts of pistachios (8·1 % g/g) or mixed nuts (7·5 % g/g) for 8 weeks would result in greater bone health in male adolescent (3 weeks; a state of continued skeletal growth) Sprague-Dawley rats. We found no difference in bone mechanical properties among groups. Tibial apparent density was ~5 % higher in the pistachio and mixed nuts groups v. control (P < 0·05) with no clear difference detected for the femur. Expressions of genes known to impact bone turnover and serum bone turnover biomarkers were unaffected by either diet relative to control. Serum antioxidant capacity was ~2-fold higher in the pistachio and mixed nuts groups compared with control (P < 0·05) but were similar between groups. Therefore, pistachios and mixed nuts may increase tibial density, in part, due to increasing antioxidant capacity. Longer dietary interventions may be necessary to elicit detectable changes in other bones (e.g. femur) and to detect potential mechanisms for the possible bone protective effects of nuts.

Increased Dietary Protein to Energy Ratio in Pre-Weaning Lambs Increases Average Daily Gain and Cortical Bone Thickness in the Tibia

The objective of this study was to examine if diets differing in crude protein (CP) to metabolizable energy (ME) ratio (CP:ME) pre-weaning altered peripheral quantitative computed tomography (pQCT) measures of bone mass and strength in lambs. The left hind leg of lambs were available at the completion of a trial designed to examine the effect that altering the CP:ME ratio in milk replacer had on growth and body composition of pre-weaned lambs reared artificially. Treatments consisted of either normal commercial milk replacer (CMR, n = 10) containing 240 g/kg CP and 21.89 MJ/kg ME, high protein milk replacer (HPM, n = 9) containing CMR with additional milk protein concentrate to reach 478.7 g/kg CP and 19.15 MJ/kg ME or a mix of normal milk replacer and milk protein concentrate adjusted twice-weekly to match optimal CP:ME requirements (MB, n = 8) based on maintenance plus 300 g/d liveweight gain. At 22 kg live weight, lambs were euthanized and the tibia including the surrounding muscle was collected and scanned using pQCT at the mid-diaphysis. Lambs on the HPM and MB diets had a greater average daily gain (p &lt; 0.01). There were limited differences in bone morphology and muscle mass, though notably the higher protein diets (MB and HPM) were associated with greater cortical thickness (p &lt; 0.05) and, therefore, potentially greater peak bone mass at maturity This finding demonstrates that pre-weaning diets, and the protein content in particular, may influence the developmental potential of long bones and attainment of peak bone mass at maturity.

Glycemic Control and Bone in Diabetes.

Purpose of ReviewThis review summarizes recent developments on the effects of glycemic control and diabetes on bone health. We discuss the foundational cellular mechanisms through which diabetes and impaired glucose control impact bone biology, and how these processes contribute to bone fragility in diabetes.Recent FindingsGlucose is important for osteoblast differentiation and energy consumption of mature osteoblasts. The role of insulin is less clear, but insulin receptor deletion in mouse osteoblasts reduces bone formation. Epidemiologically, type 1 (T1D) and type 2 diabetes (T2D) associate with increased fracture risk, which is greater among people with T1D. Accumulation of cortical bone micro-pores, micro-vascular complications, and AGEs likely contribute to diabetes-related bone fragility. The effects of youth-onset T2D on peak bone mass attainment and subsequent skeletal fragility are of particular concern.SummaryFurther research is needed to understand the effects of hyperglycemia on skeletal health through the lifecycle, including the related factors of inflammation and microvascular damage.

Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis

BackgroundGut-derived incretin hormones, including glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), regulate post-prandial glucose metabolism by promoting insulin production. GIP, GLP-1, and insulin contribute to the acute bone anti-resorptive effect of macronutrient ingestion by modifying bone turnover. Cystic fibrosis (CF) is associated with exocrine pancreatic insufficiency (PI), which perturbs the incretin response. Cross-talk between the gut and bone (“gut-bone axis”) has not yet been studied in PI-CF. The objectives of this study were to assess changes in biomarkers of bone metabolism during oral glucose tolerance testing (OGTT) and to test associations between incretins and biomarkers of bone metabolism in individuals with PI-CF. MethodsWe performed a secondary analysis of previously acquired blood specimens from multi-sample OGTT from individuals with PI-CF ages 14–30 years (n = 23). Changes in insulin, incretins, and biomarkers of bone resorption (C-terminal telopeptide of type 1 collagen [CTX]) and formation (procollagen type I N-terminal propeptide [P1NP]) during OGTT were computed. ResultsCTX decreased by 32% by min 120 of OGTT (P < 0.001), but P1NP was unchanged. Increases in GIP from 0 to 30 mins (rho = -0.48, P = 0.03) and decreases in GIP from 30 to 120 mins (rho = 0.62, P = 0.002) correlated with decreases in CTX from mins 0–120. Changes in GLP-1 and insulin were not correlated with changes in CTX, and changes in incretins and insulin were not correlated with changes in P1NP. ConclusionsIntact GIP response was correlated with the bone anti-resorptive effect of glucose ingestion, represented by a decrease in CTX. Since incretin hormones might contribute to development of diabetes and bone disease in CF, the “gut-bone axis” warrants further attention in CF during the years surrounding peak bone mass attainment.

Insulin resistance and skeletal health.

Bone fragility is a complication of type 2 diabetes (T2D), and insulin resistance is suspected to contribute to diabetes-related bone deficits. This article provides an overview of emerging clinical research involving insulin resistance and bone health by summarizing recent publications, identifying existing knowledge gaps, and suggesting 'next steps' for this evolving field of research. Clinical studies in children and adults report greater bone density in people with increased insulin resistance, but these associations are often attenuated when adjusting for body size. Advancements in bone imaging methods allow for assessment of nuanced characteristics of bone quality and strength that extend beyond standard bone mineral density assessment methods. For example, several recent studies focusing on lumbar spine trabecular bone score, a relatively new measure of trabecular bone quality from dual-energy X-ray absorptiometry, have reported generally consistent inverse associations with insulin resistance. Longitudinal studies using advanced imaging methods capable of evaluating trabecular bone microstructure and strength, such as high-resolution peripheral quantitative computed tomography, are lacking. Studies in younger individuals are sparse, but emerging data suggest that peak bone mass attainment might be threatened by diabetes progression, and increased visceral fat, suppressed muscle-bone unit, advanced glycation end-products, sedentary lifestyle, and poor diet quality might contribute to diabetes effects on bone. Prospective studies during the transition from adolescence to young adulthood are required. Insulin resistance is a main feature of T2D, which is suspected to contribute to subclinical diabetes-related threats to bone health. Future clinical studies should focus on the critical years surrounding peak bone mass and peak bone strength attainment using contemporary imaging techniques.

Bone Health in Children with Rheumatic Disorders: Focus on Molecular Mechanisms, Diagnosis, and Management.

Bone is an extremely dynamic and adaptive tissue, whose metabolism and homeostasis is influenced by many different hormonal, mechanical, nutritional, immunological and pharmacological stimuli. Genetic factors significantly affect bone health, through their influence on bone cells function, cartilage quality, calcium and vitamin D homeostasis, sex hormone metabolism and pubertal timing. In addition, optimal nutrition and physical activity contribute to bone mass acquisition in the growing age. All these factors influence the attainment of peak bone mass, a critical determinant of bone health and fracture risk in adulthood. Secondary osteoporosis is an important issue of clinical care in children with acute and chronic diseases. Systemic autoimmune disorders, like juvenile idiopathic arthritis, can affect the skeletal system, causing reduced bone mineral density and high risk of fragility fractures during childhood. In these patients, multiple factors contribute to reduce bone strength, including systemic inflammation with elevated cytokines, reduced physical activity, malabsorption and nutritional deficiency, inadequate daily calcium and vitamin D intake, use of glucocorticoids, poor growth and pubertal delay. In juvenile arthritis, osteoporosis is more prominent at the femoral neck and radius compared to the lumbar spine. Nevertheless, vertebral fractures are an important, often asymptomatic manifestation, especially in glucocorticoid-treated patients. A standardized diagnostic approach to the musculoskeletal system, including prophylaxis, therapy and follow up, is therefore mandatory in at risk children. Here we discuss the molecular mechanisms involved in skeletal homeostasis and the influence of inflammation and chronic disease on bone metabolism.

Prevalence of lactose intolerance and malabsorption among children of two ethnic groups from the urban areas of Malaysia and its relation to calcium intake and bone health status.

This study aimed to determine the prevalence of LI and lactose malabsorption (LM) in Malay and Chinese children and examine its relationship with calcium intake (CI) and BHS. A total of 400 children participated in this study. The prevalence of lactose tolerance (LT) was assessed using hydrogen breath test, LT test, and visual analogue scales. Assessment of CI was performed using a 24-h dietary recall interview (24-h DR) and food frequency questionnaire (FFQ). Calcaneal broadband ultrasound attenuation (BUA) was measured using a quantitative ultrasonometer. The prevalence of LI among Chinese children (37%) was significantly higher (p = 0.002) than among Malay children (22.5%). However, 61.5% of Malay and 54.5% of Chinese children were found to have LM. CI of the children fulfilled 30.5% and 33.9% of the Malaysian recommended CI (1300mg/day) for 24-h DR and FFQ, respectively. The BUA score of Malay children was significantly higher (p < 0.001) than that of Chinese children. However, LT and CI were not correlated with BHS (p > 0.05, respectively). LI was diagnosed among Malay and Chinese children. However, the higher prevalence of LM is rather worrying as it could develop to LI. The prevalence possibly has been worsened by insufficient CI. Thus, effective approaches to increase CI are highly needed as bone development occurs rapidly at this age and is important for the attainment of the optimum peak bone mass during late adolescence.

Bone mass and density in youth with type 2 diabetes, obesity, and healthy weight

In brief: This cross-sectional study compared bone mineral density (BMD), lean body mass and abdominal visceral fat between 180 individuals with T2DM, 226 with obesity, and 238 with normal weight, aged 10–23 years. The findings suggest that T2DM in youth may have a detrimental effect on bone accrual during the critical window of peak bone mass attainment, irrespective of obesity. Individuals with T2DM and with increased abdominal visceral fat tended to have lower BMD.

Factors associated with bone health status of Malaysian pre-adolescent children in the PREBONE-Kids Study

BackgroundModifiable lifestyle factors and body composition can affect the attainment of peak bone mass during childhood. This study performed a cross-sectional analysis of the determinants of bone health among pre-adolescent (N = 243) Malaysian children with habitually low calcium intakes and vitamin D status in Kuala Lumpur (PREBONE-Kids Study).MethodsBody composition, bone mineral density (BMD), and bone mineral content (BMC) at the lumbar spine (LS) and total body (TB) were assessed using dual-energy X-ray absorptiometry (DXA). Calcium intake was assessed using 1-week diet history, MET (metabolic equivalent of task) score using cPAQ physical activity questionnaire, and serum 25(OH) vitamin D using LC-MS/MS.ResultsThe mean calcium intake was 349 ± 180 mg/day and mean serum 25(OH)D level was 43.9 ± 14.5 nmol/L. In boys, lean mass (LM) was a significant predictor of LSBMC (β = 0.539, p < 0.001), LSBMD (β = 0.607, p < 0.001), TBBMC (β = 0.675, p < 0.001) and TBBMD (β = 0.481, p < 0.01). Height was a significant predictor of LSBMC (β = 0.346, p < 0.001) and TBBMC (β = 0.282, p < 0.001) while fat mass (FM) (β = 0.261, p = 0.034) and physical activity measured as MET scores (β = 0.163, p = 0.026) were significant predictors of TBBMD in boys. Among girls, LM was also a significant predictor of LSBMC (β = 0.620, p < 0.001), LSBMD (β = 0.700, p < 0.001), TBBMC (β = 0.542, p < 0.001) and TBBMD (β = 0.747, p < 0.001). Calcium intake was a significant predictor of LSBMC (β = 0.102, p = 0.034), TBBMC (β = 0.122, p < 0.001) and TBBMD (β = 0.196, p = 0.002) in girls.ConclusionsLM was the major determinant of BMC and BMD among pre-adolescent Malaysian children alongside other modifiable lifestyle factors such as physical activity and calcium intake.

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life.

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism (e.g., contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropin-releasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists (e.g., ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short- and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.

A six years longitudinal cohort study on the changes in bone density and bone quality up to peak bone mass in adolescent idiopathic scoliosis (AIS) with and without 2 years of Calcium and Vit-D supplementation.

Adolescent idiopathic scoliosis (AIS) is associated with osteopenia which could persist into adulthood affecting attainment of Peak Bone Mass thus resulting in osteoporosis in late adulthood. We previously reported a randomized double-blinded placebo-controlled trial(the Cal study) showing significant bone health improvement with 2-year calcium(Ca)+Vit-D supplementation for AIS girls. This study addressed the important issue whether bone health improvement from the initial 2-year Ca+Vit-D supplementation could persist as subjects approached towards Peak Bone Mass at 6-year ie after 4-year of supplement discontinuation. This was an extension of the Cal study on AIS girls (11-14 years old, mean age=12.9 years, Tanner stage<IV) with femoral neck aBMD Z-score<0 and Cobb angle≥15∘. 330 subjects were randomized to Group1(placebo), Group2(600mgCa+400-IU-Vit-D3/day) or Group3(600mgCa+800-IU-Vit-D3/day) for 2-year supplementation after which supplementation was stopped. Investigations at baseline, 2-year and 6-year included High-resolution Peripheral Quantitative Computed Tomography(HR-pQCT) at distal radius and Dual Energy X-ray Absorptiometry(DXA) at both hips. 270(81.8%) subjects completed 2-year supplementation when changes in left femoral neck aBMD, trabecular vBMD, Trabecular BV/TV, Trabecular Number and Trabecular Separation indicated significant bone health improvement with Ca+Vit-D supplementation(p<0.05). At 6-year(mean age=19.2 years), no between-group difference on bone parameters was noted except increase in Cortical Thickness being greater only in Group3 than in Group1. After 4-year supplement discontinuation, the treatment effect from the initial 2-year supplementation mostly dissipated indicating the need of continued supplementation in AIS girls to sustain therapeutic improvement on bone health as subjects approach towards Peak Bone Mass.

Bone Health in Pediatric Patients with IBD: What Is New?

Patients with inflammatory bowel disease (IBD) have increased bone fragility, demonstrated by increased fracture risk, and often have low bone density and altered bone geometry, but the underlying pathophysiology remains poorly understood. Children and adolescents with IBD appear to have decreased bone formation, at diagnosis, which frequently improves with treatment of their underlying IBD. There is a growing body of evidence regarding how the immune system interacts with bone metabolism. There are likely multi-factorial etiologies that contribute to suboptimal bone accrual and subsequent lack of peak bone mass attainment in growing patients with IBD. There appears to be differential effects dependent upon IBD sub-type and bone compartment. Pediatric patients with IBD require recognition of several risk factors that may adversely impact their bone accrual. Future studies are necessary to further delineate the effects of IBD on pediatric bone health.