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[Value of photon-absorption densitometry for the assessment of bone density].

Senile osteroporosis itself is asymptomatic unless pain is induced by the static insufficiency of the skeleton, in long lasting disease. Conventional procedures for early diagnosis and control of patients are invasive and therefore not suitable for routine purposes. The efficiency of sodium fluoride for the treatment of senile osteoporosis after a minimum of 12 months has been established by invasive methods. It is the purpose of this study, to examine the value of photoabsorption-densitometry with double-isotope-method (125-J, 241-Am) for the evaluation of a therapeutic effect in this disorder. 7 patients with clinical and radiological evidence of senile osteoporosis (6 female, 1 male patient with ages of 56 to 87 years) underwent regular follow-up examinations for one year while on a regimen of 25mg. sodium fluoride, as retard, twice daily. The bone mineral content registered 1 cm. proximal of the proc. styloideus ulnaris (representative for the trabecular bone) and 8 cm proximal from the proc. styloideus ulnaris of the right forearm (representative for cortical bone) was not statistically different from the measurements registered prior to the study. However, the bone mineral content registered in both regions increased significantly, after 12 months treatment (p less than 0.05). This indicates that the assessment of bone mineral content by photonabsorptiondensitometry is a valuable method for therapeutic control of this disorder. The method is recommended as a routine procedure for the early diagnosis and for follow up of sodium fluoride therapy geriatric patients.

Aged

Bone lesions following renal transplantation. Bone mineral density and amount of trabecular bone.

24 renal transplanted patients who developed post-transplant bone complications (aseptic necrosis of bone of spontaneous fractures) were studied and compared with a control material of age- and sexmatched renal transplanted (RT) patients. The bone mineral concentration in the forearm, histomorphometric measurements of iliac crest biopsies, and the parathyroid function were investigated. A significant reduction in the bone mineral concentration was found in the group of RT patients with bone complications compared to RT patients without. The amount of cancellous bone in the bone biopsies was reduced in patients with aseptic necrosis of bone. No significant differences in the biochemical values were found.

Adult

Pore size measurements and some age-related changes in human alveolar bone and rat femur.

Bone pore volume of pores ranging from 0.1 to 77 mum in diameter was unchanged in alveolar bone from patients with periodontal disease compared with control subjects, a finding that is inconsistent with the involvement of systemic factors in alveolar bone loss in this disease. Bone density was decreased in alveolar bone from patients with periodontal disease. Bone density of normal alveolar bone increased with age. A similar finding was obtained in rat diaphyseal bone, suggesting that this is a general phenomenon in aging bone. This could be significant inasmuch as high density bone would be expected to be more brittle. In contrast to these findings in normal alveolar bone, bone density decreased rather than increased in the 50- to 59-year-old age group in patients with periodontal disease. The cause of decreased bone density remains to be established.

Adolescent

Prevalence and predictors of low bone mineral density in pediatric inflammatory bowel disease.

OBJECTIVES: Bone health is at risk in children with inflammatory bowel disease (IBD). This study examined the prevalence and predictors of low bone mineral density (BMD) in a cohort of children and young adults with IBD. METHODS: This single-center retrospective study included patients with IBD, ages 3.5-22 years, with completed dual x-ray absorptiometry (DXA) scans from 2006 to 2019. Demographic, clinical, and laboratory data were collected. Logistic regression analysis identified predictors associated with low BMD (Z-scores&#x2009;&#x2264;&#x2009;-2 standard deviations [SDs]) for three outcomes. In an overlapping IBD cohort with available genetic data between 2002 and 2019 (n&#x2009;=&#x2009;378), genetic risk for diminished bone health was calculated using published polygenic risk scores generated from genome-wide association studies based on DXA or heel ultrasound speed of sound (SOS). Linear regression analysis examined associations of low BMD and genetic risk. RESULTS: Low BMD prevalence was 7% in our cohort (n&#x2009;=&#x2009;600) based on spine bone mineral apparent density (BMAD), which best accounts for growth delays. Median (interquartile range [IQR]) spine BMAD Z-score was -0.37&#x2009;SD (-1.11 to 0.35). Predictors of low BMAD included lower BMI Z-score (odds ratio [OR]: 0.67, p value: 0.02) and decreased height Z-score (OR: 0.6, p value: 0.005). Of those with longitudinal data (n&#x2009;=&#x2009;118), low BMI (OR: 0.44, p value: <0.001) and steroid use (OR: 3.42, p value: 0.01) were associated with suboptimal bone health (Z-scores&#x2009;&#x2264;&#x2009;-1SD). In the cohort with genetic data, heel genomic SOS (&#x3b2; [standard error] = 0.17 [0.35], p&#x2009;&#x2264;&#x2009;0.01) was associated with BMD. CONCLUSIONS: Lower BMI should prompt DXA monitoring in pediatric IBD. Genetic predisposition may identify an at-risk subpopulation.

Humans

Osteoporosis in hyperthyroidism estimated by photon absorptiometry.

The degree of osteoporosis in hyperthyroidism before and during treatment with carbimazole was studied by photon absorption technique of the right forearm and calcaneus. In addition serum total calcium, serum ionized calcium, serum phosphorus and serum alkaline phosphatase were determined. A group of 96 patients suffering from untreated hyperthyroidism (85 women and 11 men) was studied (79 of these patients were also followed during treatment) and compared to a control group of 157 persons (107 women and 50 men). The women were divided into two groups: less than or equal to 45 years old and more than 45 years old. In all groups untreated hyperthyroid patients showed lower bone densities compared to the control group, but this was only significant in women. During treatment all groups showed a significant increase in density. After 3-6 months of treatment bone density in the calcaneus increased 12% and in the forearm 1.5%; after 6 months - 3 years 33% and 31%, respectively. At that time bone density was normalized. There was no correlation between bone density in hyperthyroid patients and duration and severity of the disease. The biochemical changes were characterised by increases in serum alkaline phosphatase (26%), serum total calcium (16%) and serum ionized calcium concentration (17%) in cases of untreated hyperthyroidism. Serum phosphorus concentration did not change. A correlation was found between elevation of the alkaline phosphatase and decreased bone density.

Adult

Genetic Evidence Links Sex Hormone-binding Globulin to Total Body Bone Mineral Density at Age 45-60 Years: A Two-sample Mendelian Randomization Study.

The menopausal transition and early postmenopause represent important periods for women's skeletal health, but the genetic relevance of metabolic, behavioral, and hormone-related factors to bone mineral density during midlife remains incompletely understood. This study used publicly available genome-wide association study summary statistics to examine associations between body mass index, 25-hydroxyvitamin D, sex hormone-binding globulin, high-density lipoprotein cholesterol, smoking initiation, and alcohol intake frequency and total body bone mineral density at ages 45-60 years. Exposure genome-wide association study summary statistics were derived from large European-ancestry populations and were not restricted to midlife women, whereas the outcome genome-wide association study captured an age-stratified total body bone mineral density phenotype at age 45-60 years. This age range overlaps with the menopausal transition and early postmenopause in women. Univariable, reverse, and multivariable Mendelian randomization analyses were performed, with inverse-variance weighting as the primary method and complementary sensitivity analyses used to assess heterogeneity, pleiotropy, and result stability. Genetically predicted higher sex hormone-binding globulin was associated with lower total body bone mineral density (&#x3b2; = -0.111, 95% CI: -0.170 to -0.051; P = 0.0003). Reverse Mendelian randomization did not support reverse causation from bone mineral density to sex hormone-binding globulin. Multivariable analyses suggested that this association persisted after adjustment for selected metabolic biomarkers. The other examined exposures did not show consistent evidence of association. These findings provide genetic evidence linking sex hormone-binding globulin to total-body bone mineral density at ages 45-60 years. Further prospective and predictive studies are needed to evaluate its clinical relevance beyond established bone health assessment tools.

Humans

Uric Acid Levels Are Associated with Bone Mineral Density in Mexican Populations: A Longitudinal Study.

Background: Inconsistent epidemiological evidence between uric acid (UA) and bone mineral density (BMD) has been observed. Therefore, we evaluated the association between UA and BMD in Mexican adults. Methods: This analysis was conducted on 1423 participants from the Health Workers Cohort Study. We explored cross-sectional associations using linear regression and longitudinal associations using fixed-effects linear regression by sex and age groups (<45 and &#x2265;45 years). Results: In females <45 years old, the cross-sectional analysis showed that UA levels were positively associated with total hip BMD. However, in the longitudinal analysis, we observed a negative association with the femoral neck and lumbar spine BMD. In contrast, in males <45 years old, we found an increase in total hip and femoral neck BMD in the groups with high levels of UA in the longitudinal association. On the other hand, in females &#x2265;45 years old, we observed a longitudinal association between UA and loss of BMD at different sites. We did not observe an association between UA levels and BMD in males &#x2265;45 years old. Conclusions: Our results suggest higher serum UA levels are associated with low BMD at different skeletal sites in Mexican females. Further studies are needed to delineate the underlying mechanisms behind this observation.

Male

Sex-specific biomarkers predict bone mineral density loss at the contralateral hip after hip fracture.

OBJECTIVE: To identify inflammatory and hormonal biomarkers that predict bone loss at the contralateral (non-fractured) hip following hip fracture in males and females. METHODS: White participants who were not receiving pre-fracture glucocorticoids, sex-hormone therapy, or bone-active medications (100 males, 76 females) with hip fractures. Data were collected within 22&#xa0;days of hip fracture and at 2, 6, and 12&#xa0;months follow-up. Biomarkers were categorized into tertiles: estradiol, 25-hydroxyvitamin D3/D2, intact parathyroid hormone (iPTH), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), soluble tumor necrosis factor-&#x3b1; receptor 1, sex hormone-binding globulin, and testosterone. Femoral neck bone mineral density (BMD) at the contralateral hip was assessed, and losses exceeding the mean decline were classified as greater than average. Logistic regression models, stratified by sex, were adjusted for confounders and evaluated selected biomarker associations. RESULTS: Among males, the 2nd (OR&#xa0;=&#xa0;4.79, P&#xa0;=&#xa0;0.012) and 3rd (OR&#xa0;=&#xa0;6.36, P&#xa0;=&#xa0;0.005) IGF-1 tertiles were associated with greater odds of BMD loss than the 1st tertile. The 3rd iPTH tertile (OR&#xa0;=&#xa0;3.79, P&#xa0;=&#xa0;0.037) was similarly associated with increased odds. Among females, the 3rd (OR&#xa0;=&#xa0;0.20, P&#xa0;=&#xa0;0.031) IL-1RA tertile was associated with lower odds of BMD loss compared to the 1st tertile, while the 2nd IL-6 tertile (OR&#xa0;=&#xa0;5.99, P&#xa0;=&#xa0;0.036) was associated with higher odds. CONCLUSION: These findings suggest that inflammatory and hormonal biomarkers may be sex-specific predictors of accelerated BMD loss following hip fracture.

Biomarkers

Is there a causal relationship between resistin levels and bone mineral density, fracture occurrence? A mendelian randomization study.

BACKGROUND: In a great many of observational studies, whether there is a relevance of resistin levels on bone mineral density (BMD) and fracture occurrence has been inconsistently reported, and the causality is unclear. METHODS: We aim to assess the resistin levels on BMD and fracture occurrence within a Mendelian randomization (MR) analysis. Exposure and outcome data were derived from the Integrative Epidemiology Unit (IEU) Open genome wide association studies (GWAS) database. Screening of instrumental variables (IVs) was performed subject to conditions of relevance, exclusivity, and independence. Inverse variance weighting (IVW) was our primary method for MR analysis based on harmonized data. Weighted median and MR-Egger were chosen to evaluate the robustness of the results of IVW. Simultaneously, heterogeneity and horizontal pleiotropy were also assessed and the direction of potential causality was detected by MR Steiger. Multivariable MR (MVMR) analysis was used to identify whether confounding factors affected the reliability of the results. RESULTS: After Bonferroni correction, the results showed a suggestively positive causality between resistin levels and total body BMD (TB-BMD) in European populations over the age of 60 [&#x3b2;(95%CI): 0.093(0.021, 0.165), P = 0.011]. The weighted median [&#x3b2;(95%CI): 0.111(0.067, 0.213), P = 0.035] and MR-Egger [&#x3b2;(95%CI): 0.162(0.025, 0.2983), P = 0.040] results demonstrate the robustness of the IVW results. No presence of pleiotropy or heterogeneity was detected between them. MR Steiger supports the causal inference result and MVMR suggests its direct effect. CONCLUSIONS: In European population older than 60 years, genetically predicted higher levels of resistin were associated with higher TB-BMD. A significant causality between resistin levels on BMD at different sites, fracture in certain parts of the body, and BMD in four different age groups between 0-60 years of age was not found in our study.

Bone Density

Association between lean mass, fat mass, and waist circumference with bone mineral density in Mexican children and adolescents: a cross-sectional study.

To assess the associations of lean mass (LM), fat mass (FM), truncal fat mass (TFM), and waist circumference (WC) with bone mineral density (BMD) in Mexican youth, independently of body weight.&#xa0;We analyzed cross-sectional data from 1,054 children and adolescents from the Health Workers Cohort Study. We measured total and region-specific BMD, LM, and FM, with dual-energy X-ray absorptiometry. To eliminate the effect of body weight on FM, LM, TFM, and WC, weight-adjusted values were generated using the residuals method, and then we employed multivariate linear regression models adjusted for relevant potential confounders. We further stratified the analysis by sex, age group, and sexual maturation.&#xa0;LM was positively associated with BMD in various anatomical sites, with &#x3b2; coefficients ranging from 0.004 to 0.013 in both sexes (P&#x2009;<&#x2009;0.05). FM was inversely related to total BMD and other sites, with &#x3b2; coefficients ranging from -0.013 to -0.006 (P&#x2009;<&#x2009;0.05). WC showed negative associations with BMD at some sites, with &#x3b2; values ranging from -0.007 to -0.002. TFM was negatively associated with BMD. During puberty, the associations were consistent across all sites, whereas this was not the case for all sites after puberty. These patterns were similarly observed across different age groups.Conclusion:&#xa0;An increased LM and reduced FM are associated with higher BMD, particularly in the leg and hip regions, during childhood and adolescence, a critical developmental stage essential for healthy bone accrual and balance in adulthood.

Humans

Targeted Gene Sequencing in a Male Adult Diagnosed With X-Linked Osteoporosis Due to a Novel p.(Arg398Profs*2) PLS3 Variant.

Pathogenic loss-of-function variants in the plastin-3 gene (PLS3), encoding plastin-3 protein, are associated with early-onset X-linked osteoporosis. We present the case of a young adult male patient, with a history of multiple fragility fractures and blue sclerae, who was clinically diagnosed with osteogenesis imperfecta (OI) type 1 in childhood. He has been managed with intravenous bisphosphonate therapy, leading to an increase in bone density at the spine, stable bone density at the femoral neck, and a period free of fractures while on antiresorptive therapy. Two decades later, with a focus on reproductive family planning, a novel PLS3 variant was identified on genetic testing. This case report highlights an important role for genetic testing in patients with early-onset osteoporosis or a clinical diagnosis of OI. With the emergence of new targeted therapeutics and advanced reproductive options, such as preimplantation genetic testing, obtaining an accurate molecular diagnosis is key.

PLS3

[Comparative study of bone mineral densities in the human skeleton].

The different mineral densities and their distribution within human bone of the iliac crest, the femoral and the humeral head are analysed by microradiography with computerized photometry. 10 male and 11 female corpses between the age of 17 to 80, show that the results obtained depended upon age, sex and upon the site of the bone biopsy. Bcause of the small number of cases in this preliminary investigation, careful interpretation of these differences is mandatory. The advantages of this method are discussed.

Adolescent

The early detection of osteoporosis by Compton gamma ray spectroscopy.

The density of the distal end of the radius is one of the parameters used to determine the presence and degree of osteoporosis in patients. In this work the bone density has been determined by measuring the intensity of the Compton scattered photons, since this is proportional to the absolute density of the scatterer, in materials for which Z/A is constant. A collimated beam from a 500 mCi 137Cs source was used and the intensity of the scattered radiation measured at an angle of 90 degrees. The exact point of measurement was determined by a two-dimensional scanning technique. A plastic water phantom was used to calculate the correction needed for absorption and backscatter by the surrounding tissue. Bone density was measured by this method in 50 subjects. A good correlation was found between density of the radius and the degree of morphological change in the vertebrae. In a number of cases a low bone density was discovered without signs of osteoporosis in the spine. These findings were considered indicative of early osteoporotic change, not definable by routine X-ray techniques. This technique may be of value in the follow-up of patients and in controlling the effect of various treatment schedules.

Aged

Density and composition of trabecular and cortical bone in perinatally irradiated beagles with chronic renal failure.

Bone density and composition were studied in trabecular and cortical bone from control 2 and 4 year old beagles and those which had various degrees of renal failure as a result of perinatal irradiation. Changes in the two types of bone were qualitatively similar but consistently greater in trabecular bone. In a group identified as markedly uremic, the decrease (P less than 0.025) from control levels in specific gravity was about 4 times greater in trabecular than in cortical samples. The decrease (P less than 0.025) in grams of ash/ml was 9% in trabecular bone and 2% in cortical bone. These changes were associated with an increase (P less than 0.001) in water content and, on a percent by volume basis, approximately equal decreases in ash (P less than 0.025) and combustible matter (P less than 0.025). In a mildly uremic group there were similar trends in mean values but the only significant difference was an increase (P less than 0.001) in trabecular bone water.

Age Factors

Bone-mineral content, surface hardness, and mechanical fixation in the human radius. A correlative study.

UNLABELLED: The bone-mineral content of seventeen intact forearms from eleven cadavera was determined by the non-invasive photon-absorptiometric scanning technique (Norland-Cameron Bone-Mineral Analyzer). Each radius was then removed and three surgical screws were implanted. The forces required to push out the screws retrograde were used to represent the security of mechanical fixation and were correlated with bone-surface hardness and bone-mineral content. A high degree of correlation (r = 0.89 or more) was found between bone-mineral content and the force required for extraction. A much lower correlation existed between surface hardness and extraction force (r = 0.30). We concluded that surface hardness does not correlate well with the screw-holding capacity of bone but that bone-mineral content, as determined by a non-invasive means, does so within a 10 per cent error. CLINICAL RELEVANCE: This study demonstrates a high degree of positive correlation between bone density and the security of screw fixation in the human radius. Measuring bone density using a highly accurate, non-invasive, safe technique has clinical relevance in preoperative assessment of osteopathic patients who are being considered for internal fixation of the radius with plates and screws.

Aged