Bone Mineral Density Z-score Research Articles

Evaluation of growth, puberty, osteoporosis, and the response to long-term bisphosphonate therapy in four patients with osteoporosis-pseudoglioma syndrome.

Osteoporosis-pseudoglioma syndrome (OPPG; MIM #259770) is a rare autosomal recessively inherited disease, characterized by early-onset osteoporosis and congenital blindness, caused by loss-of-function mutations in the LRP5 gene. Beneficial effects of bisphosphonate treatment in patients with OPPG are well known, while follow-up data on growth and pubertal parameters are limited. This article provides clinical follow-up data and long-term bisphosphonate treatment results in four OPPG patients from three unrelated families, ranging between 2.5 and 7 years of age at presentation. Clinical diagnosis was molecularly confirmed in all patients, with four different germline biallelic LRP5 mutations including a novel nonsense variant c.3517C>T (p.(Gln1173*)) in two siblings with marked phenotypic variability. Anthropometric and pubertal data and bone mineral density (BMD) measurements were evaluated retrospectively. Early puberty was observed in two patients. The bisphosphonate treatment duration of patients varied around 4-7 years and improvement in BMD z-scores with bisphosphonate treatment was demonstrated in all patients (z-score changes were +5.6, +4.0, +1.0, and +1.3). Although further research is needed to identify the possible association between early puberty and OPPG, all OPPG patients should be followed up with detailed endocrinological evaluation regarding pubertal status.

Bone Alterations in Inflammatory Bowel Diseases: Role of Osteoprotegerin.

Metabolic bone disorders are one of the most frequent extra-intestinal manifestations in patients with inflammatory bowel diseases (IBD) that might result in an increase of skeletal fragility and risk of fracture. These disorders are a consequence of bone–gut crosstalk alterations, particularly due to inflammation, which involves the RANK-RANKL-Osteoprotegerin (OPG) pathway. This cross-sectional study investigates the role of serum OPG on bone health in IBD patients. In all patients, we carried out BMD measurements at the lumbar spine and femoral neck by the dual-energy X-ray absorptiometry (DXA), and evaluation of serum OPG, 25(OH)D, and PTH. We also divided all IBD patients into two groups: group 1 consisted of premenopausal women and men younger than 50 years old, while group 2 included postmenopausal women and men aged more than 50 years old. We enrolled 36 UC patients (51%), 34 CD patients (49%), and 70 healthy controls. IBD group mean age was 44 ± 17.3 years old, with a mean disease duration of 6 years. IBD patients had a mean value of OPG of 48.1 ± 26.64 pg/mL, while mean OPG in the control group was 61.35 ± 47.19 pg/mL (p < 0.05). In group 1, there was a correlation between BMD Z-scores at the lumbar spine and femoral neck and mean OPG levels in UC subjects (r = 0.47 and r = −0.21, respectively; p < 0.05), and only between Z-score at the lumbar spine and OPG level in the CD group (r = 0.83, p < 0.05). For the patients of group 2, we report a statistically significant correlation between T-score measured at the lumbar site in both UC and CD patients (r = −0.79 and r = 0.77, respectively; p < 0.05). In our study, we demonstrated serum OPG levels to be significantly decreased in IBD subjects compared to healthy age-matched individuals. However, according to our data, it seems that the measurement of serum OPG levels is not useful to better define metabolic bone disorders in IBD patients.

Bone mineral density in very low birthweight adults-A sibling study.

BackgroundChildren and adults born very low birthweight (VLBW, <1500 g) at preterm gestations have lower bone mineral density (BMD) and/or bone mineral content (BMC) than those born at term, but causality remains unknown.ObjectivesOur aim was to assess BMD and BMC in adults born at VLBW in a sibling comparison setting to account for shared genetic and environmental confounders.MethodsWe conducted a cohort study of 77 adults born VLBW and 70 same‐sex term‐born siblings at mean age of 29 years. The primary outcome variables were BMD Z‐scores, and BMC, of the femoral neck, lumbar spine, and whole body, measured using dual‐energy X‐ray absorptiometry. We analysed data by linear mixed models.ResultsThe VLBW adults had a 0.25 (95% CI 0.02, 0.47) Z‐score unit lower femoral neck BMD, and 0.35 (95% CI 0.16, 0.54) grams lower femoral neck BMC than their term‐born siblings, after adjustment for sex, age, and maternal smoking. Additional adjustment for adult body size attenuated the results. Lumbar spine, and whole body BMC were also lower in the VLBW group.ConclusionsIndividuals born at VLBW had lower BMC values at all three measurement sites, as well as lower femoral neck BMD Z‐scores, compared to term‐born siblings, partly explained by their smaller adult body size, but the differences were smaller than those reported previously with unrelated controls. This suggests that genetic or environmental confounders explain partly, but not exclusively, the association between preterm VLBW birth and adult bone mineralisation.

A proposal for the adjustment of bone mineral density for body dimensions in children.

Objectives: The precise age estimation is of high importance in bone mineral density (BMD) assessment in children, since the bone structure of a studied child is evaluated by using the age and gender dependent references. In addition, the biological age - the bone age in this case - estimation could help this bone structural evaluation process, since the developmental status of the skeletal system can significantly alter from the theoretical developmental status determined by chronological age in healthy, but early or late maturing children. The aims of the study were (1) to check whether volumetric BMD (vBMD) Z-scores estimated by considering chronological age and biological age differ significantly in children aged between 7-18 years, and (2) in the case of significant inaccuracy of Z-score estimation based on chronological age to construct new vBMD standards adjusted for body developmental status. Subjects and methods: Body structural and densitometry data of 476 healthy children aged between 7 and 18 years were used in the analysis. pQCT measurements were performed at the distal radius using Stratec XCT-2000 equipment (Stratec Inc, Germany). The centile curves of vBMD parameters were estimated by using lmsChartMaker Pro 2.3 software. Ulnar length age was used as biological age in the analysis. Results: The total and 'cortical + subcortical' vBMD changed by age in the studied age interval in both genders, while the trabecular vBMD showed significant change by age only in females. Our results confirmed that when the biological age of a child significantly differs from her/his chronological age, vBMD evaluation should be done by considering her/his biological age. Due to the increase in individual variability of rate and timing of pubertal developmental processes, the sensitivity of vBMD evaluation by considering body developmental status was the lowest in the age between 12 and 16 years in the boys and between 10 and 12 years in the girls. Therefore the suggested vBMD adjustments for biological ages are highly recommended to use at least in children with ages outside these age intervals. Conclusion: If the estimation of any biological age cannot be carried out, vBMD references adjusted for height or other body dimensions should be used in the bone health status estimation in children.

Bone mineral density and growth changes in patients with distal renal tubular acidosis after two-years treatment with a new alkalizing drug (ADV7103)

Background and objectivesADV7103 is a new prolonged-release treatment for distal renal tubular acidosis (dRTA), containing potassium citrate and potassium bicarbonate. Since acidosis may affect bone mineral contents, the effects of ADV7103 on bone mineral density (BMD) and growth in patients with dRTA over 24 months were evaluated. Patients and methodsThirty patients (24 paediatric patients and 6 adults) were included in an open-label extension study after a phase II/III trial. BMD, measured by densitometry, was assessed at baseline and at 24 months. Growth was evaluated throughout the study. Plasma bicarbonate, parathyroid hormone, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, bone alkaline phosphatase, calciuria and citraturia, were also determined. Safety and treatment compliance were evaluated as well. ResultsAfter 24 months of treatment with ADV7103, mean spine BMD z-score values significantly increased as compared with baseline (p=0.024). In adults, spine and whole-body densitometry z-scores showed a significant correlation with plasma bicarbonate levels (rS=0.82 and rS=0.97, respectively, p<0.005). There was an increase>0.5 units in z-scores for height and weight in 18% and 36% of the paediatric patients, respectively. With treatment, plasma bicarbonate concentration and calciuria at the different visits were normal in 69–86% and 93–96% patients, respectively. Only nine treatment-related gastrointestinal AEs of mild/moderate severity, were reported in five patients. ConclusionsTwo years of ADV7103 treatment improved growth and increased spine BMD. These results suggest that control of acidosis by ADV7103 treatment improves bone parameters.

Bone\xa0metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity

Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p < 0.001). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving z-score value in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.

Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders.

ContextMany different inherited and acquired conditions can result in premature bone fragility/low bone mass disorders (LBMDs).ObjectiveWe aimed to elucidate the impact of genetic testing on differential diagnosis of adult LBMDs and at defining clinical criteria for predicting monogenic forms.MethodsFour clinical centers broadly recruited a cohort of 394 unrelated adult women before menopause and men younger than 55 years with a bone mineral density (BMD) Z-score < -2.0 and/or pathological fractures. After exclusion of secondary causes or unequivocal clinical/biochemical hallmarks of monogenic LBMDs, all participants were genotyped by targeted next-generation sequencing.ResultsIn total, 20.8% of the participants carried rare disease-causing variants (DCVs) in genes known to cause osteogenesis imperfecta (COL1A1, COL1A2), hypophosphatasia (ALPL), and early-onset osteoporosis (LRP5, PLS3, and WNT1). In addition, we identified rare DCVs in ENPP1, LMNA, NOTCH2, and ZNF469. Three individuals had autosomal recessive, 75 autosomal dominant, and 4 X-linked disorders. A total of 9.7% of the participants harbored variants of unknown significance. A regression analysis revealed that the likelihood of detecting a DCV correlated with a positive family history of osteoporosis, peripheral fractures (> 2), and a high normal body mass index (BMI). In contrast, mutation frequencies did not correlate with age, prevalent vertebral fractures, BMD, or biochemical parameters. In individuals without monogenic disease-causing rare variants, common variants predisposing for low BMD (eg, in LRP5) were overrepresented.ConclusionThe overlapping spectra of monogenic adult LBMD can be easily disentangled by genetic testing and the proposed clinical criteria can help to maximize the diagnostic yield.

Mechanical-Stress-Related Epigenetic Regulation of ZIC1 Transcription Factor in the Etiology of Postmenopausal Osteoporosis.

Mechanical loading exerts a profound influence on bone density and architecture, but the exact mechanism is unknown. Our study shows that expression of the neurological transcriptional factor zinc finger of the cerebellum 1 (ZIC1) is markedly increased in trabecular bone biopsies in the lumbar spine compared with the iliac crest, skeletal sites of high and low mechanical stress, respectively. Human trabecular bone transcriptome analyses revealed a strong association between ZIC1 mRNA levels and gene transcripts characteristically associated with osteoblasts, osteocytes and osteoclasts. This supposition is supported by higher ZIC1 expression in iliac bone biopsies from postmenopausal women with osteoporosis compared with age-matched control subjects, as well as strongly significant inverse correlation between ZIC1 mRNA levels and BMI-adjusted bone mineral density (BMD) (Z-score). ZIC1 promoter methylation was decreased in mechanically loaded vertebral bone compared to unloaded normal iliac bone, and its mRNA levels correlated inversely with ZIC1 promoter methylation, thus linking mechanical stress to epigenetic control of gene expression. The findings were corroborated in cultures of rat osteoblast progenitors and osteoblast-like cells. This study demonstrates for the first time how skeletal epigenetic changes that are affected by mechanical forces give rise to marked alteration in bone cell transcriptional activity and translate to human bone pathophysiology.

Bone mineral density (BMD) and neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in childhood thyroid diseases.

This study aimed at investigating the laboratory parameters related to the pathogenesis of bone loss, including bone mineral density (BMD), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in children with thyroid disease and healthy controls. Children and adolescents with hypothyroidism (n=63) and hyperthyroidism (n=30) as well as 32 age- and sex-matched healthy controls were included in the study. Auxological data, BMD, hemogram parameters, the levels of thyroid hormone, thyroid stimulating hormone (TSH), thyroid autoantibodies, parathyroid hormone, 25-hydroxy vitamin D, alkaline phosphatase, calcium, and phosphorus were analyzed. The mean age of the patients was 12.12±2.7 years (range: 8-17). BMD Z-scores were within the normal range in all the patients and healthy controls. The BMD Z-scores were significantly higher in patients with hyperthyroidism than those in the control group and in patients with hypothyroidism. No significant difference was observed between the control and hypothyroid groups in terms of the BMD Z-scores. A correlation was observed between the BMD Z-scores and NLR, MLR, PLR, and free T4 levels. In patients with hypothyroidism, the BMD Z-scores were significantly positively correlated with the NLR, MLR, PLR, and the TSH level. In the control group, there was a moderate positive correlation between the BMD Z-scores and NLR. In the hyperthyroid group, there were no significant correlations between the BMD Z-scores and other variables. The study data suggest that in children and adolescents with thyroid disease, the relationship between the BMD Z-scores and NLR, MLR, and PLR at the initial diagnosis in the hypothyroidism group was different from that in their healthy peers.

Bone microarchitecture impairment in prolactinoma patients assessed by HR-pQCT.

Prolactinoma may reduce bone mineral density (BMD) and increase fracture risk, but its influence on bone microarchitecture remains to be elucidated. The purpose of this study is to evaluate bone microarchitecture parameters by high-resolution peripheral quantitative computed tomography (HR-pQCT) in prolactinoma patients. 31 prolactinoma patients and 62 age- and sex-matched healthy controls in our center were included, and HR-pQCT was used to evaluate their bone microarchitecture at the radius and tibia. Z-scores for bone microarchitecture parameters were calculated based on previously published reference. After adjusting for height and weight, prolactinoma patients had lower trabecular (- 0.011mm, p = 0.005) and cortical thickness (- 0.116mm, p = 0.008) and cortical area (- 6.0 mm2, p = 0.013) at radius, as well as lower trabecular (- 0.014mm, p = 0.008) and cortical (- 0.122mm, p = 0.022) thickness at tibia compared with the controls. Patients with higher prolactin level had more severe bone microarchitecture impairments. After adjusting for prolactin level and age, male patients had lower trabecular volumetric BMD (vBMD), trabecular number, trabecular thickness, and cortical porosity at radius, as well as lower trabecular vBMD, trabecular bone volume fraction, trabecular number, and cortical area, and higher trabecular separation at tibia compared with female patients. Z-score for radius vBMD was correlated with Z-score for areal BMD (aBMD) at lumbar and femoral neck, while Z-score for tibia vBMD was correlated with Z-score for lumbar aBMD, and some patients with vBMD Z-score below - 2.0 had aBMD Z-score within normal range. Peripheral bone microarchitecture was impaired in prolactinoma patients, especially in patients with higher prolactin level. We compared the bone microarchitecture of prolactinoma patients and healthy controls by high-resolution peripheral quantitative computed tomography (HR-pQCT), and found that many bone microarchitecture parameters were impaired among prolactinoma patients. Such impairment was more prominent among patients with higher prolactin level.

Open-Label Pilot Study of Interferon Gamma-1b in Patients With Non-Infantile Osteopetrosis.

ABSTRACTThe only treatment currently available for patients with severe infantile osteopetrosis is hematopoietic cell transplantation (HCT). HCT‐related toxicity and mortality risks typically preclude its use in non‐infantile patients, and other therapies are needed for these patients who have significant disease‐related morbidity. Interferon gamma‐1b is currently approved by the U.S. Food and Drug Administration (FDA) for treatment of severe infantile osteopetrosis (autosomal recessive osteopetrosis [ARO]). However, little is known about the effects of interferon gamma‐1b in non‐infantile osteopetrosis. Thus, this pilot study aimed at testing the safety and tolerability of interferon gamma‐1b in patients with non‐infantile osteopetrosis and assessing the clinical effects. We performed a 12‐month, open‐label, multi‐center pilot study involving patients >1 year‐old diagnosed radiographically with osteopetrosis. Patients were initiated on interferon gamma‐1b subcutaneously 15 μg/m2 three times weekly, to be titrated over 3 weeks to a goal of 100 μg/m2 three times weekly. The primary aim was safety and tolerability. The secondary aims were to assess changes in peripheral quantitative computed tomography (pQCT), dual‐energy x‐ray absorptiometry (DXA) bone mineral density (BMD) Z‐scores, bone biomarkers, and quality‐of‐life (QOL) measures. Four of the five participants enrolled withdrew from the study between 3 and 9 months due to intolerability of interferon gamma‐1b–related flu‐like symptoms. The last participant completed the study with the addition of prednisone on days of interferon gamma‐1b administration. DXA and pQCT outcomes were stable over 6–12 months, and there were no clear trends in bone biomarkers or QOL measures. No serious drug‐related adverse events were reported during this study. Interferon gamma‐1b was only tolerable in one of five participants with the addition of prednisone. The stabilization of BMD and other measures of bone health during this study suggest possible positive effects of interferon gamma‐1b on osteopetrosis; however, additional data are needed before conclusions on treatment efficacy can be made. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Prevalence of Female Athlete Triad Risk Factors among Female International Volunteers and College Age-Matched Controls.

This study retrospectively compared the prevalence of factors related to the female athlete triad (low energy availability, secondary amenorrhea (SA), low bone mineral density (BMD)), and post-study BMD of female college students and female international volunteer missionaries (volunteers). Female college students (21–26 years) completed a survey that retrospectively assessed an 18-month study period (volunteer service or first 18 months of college); Diet History Questionnaire III (DHQ III) and Dual-Energy X-ray Absorptiometry (DXA) scan were optional. One-way ANOVAs and chi-squared distributions assessed group differences. Logistic regression assessed covariates of SA and BMD; corresponding odds ratios (OR) and confidence intervals (CI) were calculated. Statistical significance was set at p < 0.001. 3683 participants (58.8% volunteers, 31.5% non-volunteers, 9.8% others) provided complete survey data; 246 completed the DHQ III, and 640 had a post-study DXA scan. Volunteers had higher metabolic equivalent (MET) hours than non-volunteers and others (p < 0.001), and higher prevalence of food insecurity (p < 0.001) and SA (p < 0.001). Volunteers had higher odds of SA (OR = 2.17, CI = 1.75–2.62) than non-volunteers. Weight loss, body satisfaction, “other” weight loss methods, increased MET hours, and vomiting during the study period increased participants’ odds of SA. Participants’ average BMD Z-scores were within the expected range at all sites, with no significant group differences. Volunteers’ higher MET hours and higher prevalence of food insecurity and SA did not result in significantly lower post-study period BMD.

BONE HEALTH AND GROWTH IN SPINAL MUSCULAR ATROPHY TYPE 2 AND 3

Objective: Spinal muscular atrophy is a lower motor neuron disease, but other parts of the body could be affected. This study compared bone mineral density with bone metabolism and physical growth rates in patients diagnosed with spinal muscular atrophy type 2 and type 3. Material and Methods: Twenty-six patients with spinal muscular atrophy were included in the study (15 patients for type 2 and 11 for type 3). Weights and heights of patients were measured, standard deviation scores were determined, and the body-mass index was calculated. Motor function and pubertal assessment were performed. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin vitamin D levels were compared. Spine radiography for scoliosis and bone densitometry for bone mineral density were performed, and volumetric bone mineral density was calculated for age and sex. Results: Medians of height standard deviation scores were significantly lower in type 2 patients. There was no difference between the two groups in terms of serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin D levels. The ratio of scoliosis was higher in type 2 patients as was its severity, but Z-scores of volumetric bone mineral density was lower in the same group. Conclusion: This study showed that bone mineralization and growth rates were significantly lower in spinal muscular atrophy, mainly in type 2. Further studies are needed to evaluate bone health in spinal muscular atrophy patients.

BONE HEALTH AND GROWTH IN SPINAL MUSCULAR ATROPHY TYPE 2 AND 3

Objective: Spinal muscular atrophy is a lower motor neuron disease, but other parts of the body could be affected. This study compared bone mineral density with bone metabolism and physical growth rates in patients diagnosed with spinal muscular atrophy type 2 and type 3. Material and Methods: Twenty-six patients with spinal muscular atrophy were included in the study (15 patients for type 2 and 11 for type 3). Weights and heights of patients were measured, standard deviation scores were determined, and the body-mass index was calculated. Motor function and pubertal assessment were performed. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin vitamin D levels were compared. Spine radiography for scoliosis and bone densitometry for bone mineral density were performed, and volumetric bone mineral density was calculated for age and sex. Results: Medians of height standard deviation scores were significantly lower in type 2 patients. There was no difference between the two groups in terms of serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25-hydroxyvitamin D levels. The ratio of scoliosis was higher in type 2 patients as was its severity, but Z-scores of volumetric bone mineral density was lower in the same group. Conclusion: This study showed that bone mineralization and growth rates were significantly lower in spinal muscular atrophy, mainly in type 2. Further studies are needed to evaluate bone health in spinal muscular atrophy patients.

Associations of pregnancy phthalate concentrations and their mixture with early adolescent bone mineral content and density: The Health Outcomes and Measures of the Environment (HOME) study.

The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females. In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

Evaluation of bone mineral density in patients with gestational diabetes mellitus by ultrasonic bone mineral density measurement combined with Vitamin-D deficiency and analysis of influencing factors.

Objectives:To investigate the evaluation of bone mineral density (BMD) in patients with gestational diabetes mellitus (GDM) by ultrasonic bone mineral density measurement combined with Vitamin-D deficiency and its influencing factors.Methods:A total of 100 patients with gestational diabetes mellitus (GDM) admitted to our hospital from January 2017 to December 2020 were selected as the GDM group, and another 100 pregnant volunteers who underwent physical examination in our hospital were selected as the healthy control group. The levels of triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), glycated hemoglobin (HbA1c), fasting insulin (FINS), C-peptide, procollagen, parathyroid hormone (PTH), serum calcium, 25-hydroxyvitamin-D3 (25-OH-D) and ultrasonic BMD Z-score were determined and compared between the two groups. Moreover, the effects of different levels of 25-OH-D on the above indexes were compared, and multivariate logistic regression analysis was performed.Results:Compared with the healthy reference group, the levels of TG, TC, LDL-C, PTH, HbA1c, FINS and C-peptide of GDM group were significantly increased (P < 0.05), while BMD Z-score and 25-OH-D levels were significantly decreased. In the GDM group, the lower the 25-OH-D levels, the higher the FPG, HbA1c and FINS levels and the lower the serum calcium level and BMD Z-score, with statistically significant differences (P < 0.05). Multivariate logistic regression analysis showed that 25-OH-D was an independent risk factor affecting BMD in patients with GDM (P<0.05).Conclusions:Patients with GDM have lower BMD and 25-hydroxyVitamin-D3 levels. Measurement of BMD and 25-hydroxyVitamin-D3 levels can help assess the progression of GDM. BMD has a close bearing on Vitamin-D deficiency in patients with GDM.

Evaluation of nutritional status and related factors in children with cystic fibrosis.

This study aimed to evaluate the nutritional status and body composition in children with cystic fibrosis (CF), in accordance with the new nutritional targets defined by European Society for Clinical Nutrition and Metabolism (ESPEN), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Cystic Fibrosis Society (ECFS) 2016. In this cross-sectional study, data were collected prospectively in a single centre. A record was made for a total of 95 patients with CF of clinical data. Anthropometric data were evaluated using the World Health Organization growth standards. The bone mineral density (BMD) z-score was adjusted for height by measuring dual-energy X-ray absorptiometry (DXA). The speed of sound z-score values were measured with quantitative ultrasound (QUS). The nutritional status was normal in 37.9% of patients aged < 2 years and 33.3% of patients aged 2-18 years. When the DXA BMD z-score values were corrected for height, it was determined that the BMD deficit was less. The calcaneus QUS SOS z-score mean value was lower than the mean height for age z-score adjusted BMD (BMDHAZ). The malnutrition rates of CF patients were higher than the rates previously reported in literature. As there are insufficient nutritional data in Turkey, there is a need for multi-centre studies to determine the frequency of malnutrition according to the new classifications. It is clear that QUS measurements cannot replace DXA in the diagnosis of osteopenic bone disease. However, when low values are determined with QUS as the first recommended measurement in the screening of bone status, it can be considered appropriate to confirm the status with DXA.

Evaluation of endocrine functions before and after enzyme replacement therapy in children with mucopolysaccharidosis

There is a scarcity of data concerning endocrine function and the effects of enzyme replacement therapy (ERT) on growth and other endocrine functions in patients with mucopolysaccharidosis (MPS). This study retrospectively evaluated height increase, bone mineral density (BMD), and other endocrine functions in MPS patients who received ERT for at least two years in our clinic. The clinical findings, hormonal analysis (TSH, fT4, ACTH, cortisol, FSH, LH, testosterone, estradiol, prolactin, GH, IGF-1, IGFBP-3), and BMD measurements of 10 MPS patients, aged 0-18 years, before and after ERT were recorded and compared retrospectively. Four patients were MPS Type-2, five were MPS Type-4, and one was MPS Type-6. Nine of the patients were male, and one was female. The mean treatment onset age was 7.6 years. The mean ± standard deviation of the patients' height SDS was -4.61±3.01 before treatment and -5.65±2.42 after treatment. While the mean BMD Z-score of the patients was -2.33±1.77 before treatment, it was -0.94±1.52 after treatment. Apart from growth retardation (one of the most prominent disease features), no severe dysfunction was detected in other endocrine organs in our patients with MPS. Severe short stature was evident at the time of diagnosis in MPS patients, and their height SDS worsened, despite ERT. However, osteoporotic BMD Z-scores at diagnosis improved after ERT. No serious dysfunction was seen in other endocrine organs.

Bone Health in Pediatric Fracture Patients: A DEXA Study

Vitamin D deficiency is widespread in children and is associated with increased fracture severity. Previous studies have shown mixed results on the impact of vitamin D supplementation on bone health parameters measured on dual-energy x-ray absorptiometry (DEXA) scan. This is the first longitudinal DEXA study in a pediatric fracture population. Pediatric fracture patients with vitamin D levels below 20 ng/mL were counseled to take vitamin D and calcium per a serum-based protocol. Patients underwent baseline DEXA within the initial 12 weeks post fracture and had follow-up scans at 6 and 12 months. 48 patients were enrolled, 32 patients completed two DEXA scans, and 19 completed three DEXA scans. There was a significant increase in lumbar spine BMC, TBLH BMD, and TBLH BMC between DEXA 1 and 2 (p 0.001). A positive trend in DEXA parameters is suggested between DEXA 1 and DEXA 3. Height adjusted z-scores (HAZ) were calculated which showed no statistical significance, p-values > 0.05. In this group, there are no significant changes in TBLH, BMC or BMD z-scores one year after fracturing despite vitamin D and calcium supplementation. This suggests that children returning to collision sports may be at continued risk for refracture and future studies are needed.

Efficacy and safety of bisphosphonates on childhood osteoporosis secondary to chronic illness or its treatment: a meta-analysis.

Background:Bisphosphonates are a type of medication that prevents the loss of bone density. Secondary childhood osteoporosis reduces bone strength and results in an increased risk of fragility fracture. This meta-analysis aims to explore the efficacy and safety of bisphosphonates on secondary childhood osteoporosis.Methods:We performed a systematic search of PubMed, Cochrane library, and Web of Science databases up to 31 July 2022 to screen for random clinical trials (RCTs) on bisphosphonate treatment for childhood secondary osteoporosis. Data from selected studies, mainly changes in lumbar spine (LS) bone mineral density (BMD), changes in LS BMD Z-scores, fracture events, and adverse events (AEs), were extracted and analyzed.Results:Nine RCTs (n = 429 in total) were included in our meta-analysis. The meta-analysis indicated that bisphosphonates improved the changes in LS BMD [mean difference (MD) = 0.04, 95% confidence intervals (CIs) = 0.01–0.07, p < 0.01] and LS BMD Z-scores [MD = 0.52, 95% CI = 0.23–0.81, p < 0.01]. Use of bisphosphonates did not increase the risk of AEs [odds ratio (OR) = 1.61, 95% CI = 0.87–2.99, p = 0.13]. Subgroup analysis showed that routes of administration, but not causes of secondary osteoporosis, might influence the efficacy of bisphosphonates. IV bisphosphonates close to significantly improved the incidence of fracture (OR = 0.34, 95% CI: 0.11–1.08, p = 0.07).Conclusions:The use of bisphosphonates improves LS BMD without increasing AE rates, which supports the clinical use of bisphosphonates in secondary childhood osteoporosis. Further large RCTs are still warranted, especially for their long-term effects on fracture rates.