Bone Health Research Articles

Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has profound adverse effects on bone health and homeostasis. MASLD appears to be associated with changes in bone mineral density (BMD) and fracture rate. However, the data are ambiguous and conflicting. Although several studies have shown that children and adolescents with MASLD have decreased BMD, the data on the prevalence of fragility fractures among children are scarce. In adults, increasing evidence suggests that MASLD decreases BMD and increases the risk of fragility fractures, which appears to be due to deterioration of bone architecture in addition to a decrease in BMD. Effects of MASLD on bone health may also be age- and race-specific. MASLD does not seem to increase fracture risk in children and adolescents but increases the risk of fractures in elderly men, especially those of Asian origin. From a mechanistic perspective, bone remodeling is a continuous process between osteoblasts (bone-forming) and osteoclasts (bone-resorbing), with any imbalance resulting in metabolic bone disease. In individuals with MASLD, loss of anabolic insulin receptor signaling (insulin resistance) in osteoblasts and increased receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL) signaling in osteoclasts (proinflammatory cytokines) swings the pendulum toward accelerated bone loss. These processes are further complicated by the concomitant presence of obesity, type 2 diabetes mellitus, or sarcopenia in individuals with MASLD. This study reviews the current literature associated with the effects of MASLD on BMD and fragility fractures in children/adolescents and adults. This review also discusses the pathomechanisms that link MASLD with changes in BMD and fragility fractures.

Hypervitaminosis D Due to Overdose: A Case Series

Abstract Vitamin D, a fat-soluble vitamin, is found in many animal products and fortified foods and is endogenously made in the human body. Vitamin D supplementation has become a part of the routine prescription; its continuous intake without any follow-up has led to hypervitaminosis D due to overdosing. Hypercalcemia accompanies hypervitaminosis D, affecting bone health, blood pressure, and kidney function. We studied six cases that landed in hypervitaminosis D due to prolonged intake.

PoCOsteo: generic novel platform for bone turnover marker measurement & monitoring.

Despite the increasing efforts in improving bone health assessments, current diagnostics suffer from critical shortcomings. The present article therefore describes a multiplex label-free immunosensor designed and validated for the assessment of two bone turnover markers (BTMs), namely beta isomerized C-terminal telopeptide of type I collagen (CTx) and Procollagen I Intact N-Terminal (PINP), the combination of which is needed to illustrate an accurate overview of bone health. The immunosensor was then tested outside and inside of a microsystem, with the aim of becoming compatible with a point of care system fabricated for automated assessment of these biomarkers later-on at patient side. Custom-made monoclonal antibodies were specifically designed for this purpose in order to guarantee the selectivity of the immunosensor. In the final platform, a finger prick blood sample is introduced into the microfluidic manifolds without any need for sample preparation step, making the tool suitable for near patient and outside of the central laboratory applications. The platform was exploited in 30 real blood samples with the results validated using electrochemiluminescence immunoassay. The results revealed the platform was capable of measuring the target analyte with high sensitivity and beyond the recommended clinical reference range for each biomarker (CTx: 104-1028 ng L-1 and PINP: 16-96 μg L-1, correspondingly). They also showed the platform to have a limit of detection of 15 (ng L-1) and 0.66 (μg L-1), a limit of quantification of 49 (ng L-1) and 2.21 (μg L-1), and an inter- and intra-assay coefficient of variance of 5.39-6.97% and 6.81-5.37%, for CTx and PINP respectively, which is comparable with the gold standard. The main advantage of the platform over the state-of-the art was the capability of providing the results for two markers recommended for assessing bone health within 15 minutes and without the need for skilled personnel or costly infrastructure.

Persistent changes in calcium-regulating hormones and bone turnover markers in living kidney donors more than 20 years after donation

Abstract In a previous study, we observed decreased 1,25-dihydroxyvitamin D levels, secondary hyperparathyroidism, and increased bone turnover markers in living kidney donors (LKDs) at 3 months and 36 months after kidney donation. In our recent survey-based study, we found no increased risk of fractures of all types but observed significantly more vertebral fractures in LKDs compared to matched controls. To elucidate the long-term effects of kidney donation on bone health, we recruited 139 LKDs and 139 age and sex matched controls from the survey-based participants for further mechanistic analyses. Specifically, we assessed whether LKDs had persistent abnormalities in calcium and phosphorus-regulating hormones and related factors, in bone formation and resorption markers, and in density and microstructure of bone compared with controls. We measured serum markers, bone mineral density (BMD), bone microstructure and strength (via high-resolution peripheral quantitative computed tomography and micro-finite element analysis [HRpQCT]), and advanced glycation end-products (AGEs) in donors and controls. LKDs had decreased 1,25-dihydroxyvitamin D concentrations (donors mean 33.89 pg/mL vs. controls 38.79 pg/mL, percent difference = -12.6%; P < 0.001), increases in both parathyroid hormone (PTH when corrected for ionized calcium; donors mean 52.98 pg/mL vs. controls 46.89 pg/mL,% difference 13%; P = 0.03) and ionized calcium levels (donors mean 5.13 mg/dL vs. controls 5.04 mg/dL; P < 0.001) and increases in several bone resorption and formation markers versus controls. LKDs and controls had similar measures of BMD; however, HRpQCT suggested that LKDs have a statistically insignificant tendency towards thinner cortical bone and lower failure loads as measured by micro-finite element analysis. Our findings suggest that changes in the hormonal mileu after kidney donation and the long-term cumulative effects of these changes on bone health persist for decades after kidney donation and may explain later-life increased rates of vertebral fractures.

Excess glucose alone depress young mesenchymal stromal/stem cell osteogenesis and mitochondria activity within hours/days via NAD+/SIRT1 axis

BackgroundThe impact of global overconsumption of simple sugars on bone health, which peaks in adolescence/early adulthood and correlates with osteoporosis (OP) and fracture risk decades, is unclear. Mesenchymal stromal/stem cells (MSCs) are the progenitors of osteoblasts/bone-forming cells, and known to decrease their osteogenic differentiation capacity with age. Alarmingly, while there is correlative evidence that adolescents consuming greatest amounts of simple sugars have the lowest bone mass, there is no mechanistic understanding on the causality of this correlation.MethodsBioinformatics analyses for energetics pathways involved during MSC differentiation using human cell information was performed. In vitro dissection of normal versus high glucose (HG) conditions on osteo-/adipo-lineage commitment and mitochondrial function was assessed using multi-sources of non-senescent human and murine MSCs; for in vivo validation, young mice was fed normal or HG-added water with subsequent analyses of bone marrow CD45− MSCs.ResultsBioinformatics analyses revealed mitochondrial and glucose-related metabolic pathways as integral to MSC osteo-/adipo-lineage commitment. Functionally, in vitro HG alone without differentiation induction decreased both MSC mitochondrial activity and osteogenesis while enhancing adipogenesis by 8 h’ time due to depletion of nicotinamide adenine dinucleotide (NAD+), a vital mitochondrial co-enzyme and co-factor to Sirtuin (SIRT) 1, a longevity gene also involved in osteogenesis. In vivo, HG intake in young mice depleted MSC NAD+, with oral NAD+ precursor supplementation rapidly reversing both mitochondrial decline and osteo-/adipo-commitment in a SIRT1-dependent fashion within 1 ~ 5 days.ConclusionsWe found a surprisingly rapid impact of excessive glucose, a single dietary factor, on MSC SIRT1 function and osteogenesis in youthful settings, and the crucial role of NAD+—a single molecule—on both MSC mitochondrial function and lineage commitment. These findings have strong implications on future global OP and disability risks in light of current worldwide overconsumption of simple sugars.

Bone health and awareness of osteoporosis in women aged 40 to 60 years in Jiaxing City, China.

The objective of this study is to evaluate the pattern of bone mineral density (BMD) in native Jiaxing women, and to investigate their awareness of osteoporosis. A total of 538 native Jiaxing women aged 40 to 60 years were recruited from January 2022 to December 2023 when they had routine examinations in the physical examination center of Jiaxing Maternal and Child Health Hospital. The Chinese version of Osteoporosis Prevention and Cognition Tool was used to evaluate participants' cognitive level of osteoporosis. BMD of participants' lumbar spine (L1-L4) and left hip (Neck/Troch/Ward) was measured by dual-energy X-ray absorptiometry. The mean total score of the awareness about osteoporosis (general knowledge, complications, and prevention) was 22.08 ± 2.74, which was suboptimal. The higher the education level, the higher the score of awareness (P < .01). Medical staff had the highest awareness rate of osteoporosis and the farmer had the lowest. Lumber spine and hip BMD of all sites was significantly decreased with increasing age (P < .001). Premenopausal women had higher BMD than postmenopausal women at all lumbar spine and hip sites (P < .01). The overall frequency of osteoporosis was 10.8% in the lumbar spine, 8.6% in the total hip, and 17.7% in either site. Osteoporosis and osteopenia are highly prevalent among native Jiaxing women but their awareness of osteoporosis is inadequate. To reduce the prevalence of osteoporosis, especially among the unemployed, we should carry out effective health education through multimedia to raise their awareness of osteoporosis. In addition, menopausal hormone therapy should also be considered in menopausal women.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Citrate-based dietary alkali supplements available in Germany: an overview

BackgroundFruits and vegetables are abundant in alkali precursors and effectively reduce the Potential Renal Acid Load (PRAL) from diet. Oral alkali supplements are supposed to exert comparable alkalizing effects on the human body, and have been shown to beneficially affect bone and kidney health. A comparative analysis of the available dietary alkali supplements in Germany was performed, contrasting their potential PRAL-lowering potential.MethodsWe reviewed the currently available dietary citrate-based alkali supplements sold in Germany with a special focus on their mineral content, their PRAL-lowering potential and other characteristics inherent to each product. Supplements containing either potassium-, calcium- or magnesium citrate or any combination of these organic salts were reviewed. The total alkali load (TAL) was calculated based on the recommended daily dosage (RDD).ResultsSixteen supplements with a mean alkali powder content of 220.69 ± 111.02 g were identified. The mean magnesium content per RDD was 239.93 ± 109.16 mg. The mean potassium and median calcium content were 550 ± 325.58 mg and 280 (240) mg, respectively. Median TAL was 1220 (328.75) mg. The PRAL-lowering potential from a single RDD ranged from − 51.65 mEq to -8.32 mEq. Substantial price differences were found, and the mean price of the examined supplements was 16.67 ± 5.77 Euros. The median price for a 1 mEq PRAL-reduction was 3.01 (3.14) cents, and ranged from 0.77 cents to 10.82 cents.ConclusionsNoticeable differences between the identified alkali supplements were encountered, warranting an individual and context-specific approach in daily clinical practice.

Clinical and Demographic Characteristics of Pyruvate Kinase Deficiency Patients: A Comprehensive Case Series Analysis.

Introduction Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder characterized by mutations in the PKLR gene, causing impaired glycolysis in red blood cells and leading to diverse clinical manifestations. The prevalence of PKD in Saudi Arabia remains understudied, particularly in the context of consanguinity and non-specialized medical facilities. Methods We conducted a retrospective analysis of seven PKD patients of Arab ethnicity, focusing on demographics, medical history, clinical features, laboratory results, treatments, and outcomes. Results Our patient cohort comprised five males and two females, aged 10 to 38 years, of Arab ethnicity. Consanguinity was prevalent, and hereditary connections were identified in five patients. PKD exhibited varying clinical presentations, with early-onset symptoms including neonatal jaundice and symptomatic anemia. One patient experienced severe hepatic disease progression leading to multiorgan failure. Blood transfusions were universally required, indicating the severity of the disorder. Anemia severity varied among patients, with diverse hematological irregularities. Splenectomy was performed for most patients, improving hemoglobin levels and transfusion needs in some cases. Iron chelation was administered, although iron overload persisted. Thrombocytosis and venous thromboembolism were observed post splenectomy. Jaundice and gallstones were common, leading to cholecystectomy. Laboratory findings remained consistent, with heightened reticulocyte counts and altered enzyme levels. Discussion PKD is a rare disorder characterized by diverse clinical manifestations. Prevalence estimation is complex due to various factors, and its diagnosis is challenged by clinical similarities with other disorders. Our cohort exhibited a spectrum of complications, highlighting the necessity for tailored interventions. Iron overload remained a concern, necessitating continuous monitoring. Although endocrine disorders and osteoporosis were absent in our cohort, vigilance is essential due to the disease's progressive nature. Genetic factors were prominent, supporting the genetic basis of PKD. Splenectomy improved anemia but had a limited impact on gallstones. Iron overload management and bone health remain crucial considerations. Conclusion This study offers comprehensive insights into the clinical and demographic characteristics of PKD patients, illustrating the complex nature of the disorder. The findings underscore the need for personalized management strategies and vigilant monitoring to address the diverse clinical manifestations and challenges associated with PKD.

Cardiovascular and bone health outcomes in older people with subclinical hypothyroidism treated with levothyroxine: a systematic review and meta-analysis

BackgroundThyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes.MethodsA systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected.ResultsSix articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71–1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible.ConclusionsThis systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years.Systematic review registrationPROSPERO CRD42022308006

Performance and bone health of broilers reared under artificial lighting and supplemented with different levels of vitamin D3

Performance and bone health of broilers reared under artificial lighting and supplemented with different levels of vitamin D3

Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives.

Vitamin D, acknowledged since the 1930s for its role in preventing rickets, gained additional prominence in relation to fragility fracture prevention in the late 1980s. From the early 2000s, connections between vitamin D deficiency and extra-skeletal pathologies emerged, alongside increased awareness of widespread deficits. This prompted crucial debates on optimal serum concentrations, expected to conclude when the outcomes of high-dose supplementation randomized controlled trials were available. Skepticism arose with inconclusive results from these trials. This review begins with an exploration of vitamin D metabolism, followed by a detailed description of the measurement of vitamin D metabolites and the crucial role of standardization. Subsequent sections focus on the association of vitamin D with bone health and explore the extra-skeletal effects. The review concludes with a comprehensive discussion on the definition of vitamin D status and its implications for supplementation. Despite standardization efforts, assay variations and challenges still exist, especially in specific patient groups. Vitamin D supplementation has a significant impact on bone metabolism and optimal vitamin D status improves the efficacy of antiresorptive drugs such as bisphosphonates. The extra-skeletal effects of vitamin D remain debated, but may include potential benefits in conditions such as respiratory infections and cancer mortality, particularly in deficient individuals. The definition of vitamin D sufficiency is nuanced, especially when variations in population groups and analytical methods are taken into account. Despite ongoing debates and recent mega-trials tempering enthusiasm, vitamin D remains a complex and essential element in human health. Further research is needed to clarify its role in various health outcomes and guide supplementation strategies.

Hypopituitarism and bone disease: pathophysiology, diagnosis and treatment outcomes.

Hypopituitarism is a rare but significant endocrine disorder characterized by the inadequate secretion of one or more pituitary hormones. The intricate relationship between hypopituitarism and bone health is a topic of growing interest in the medical community. In this review the authors explore associations between hypopituitarism and bone health, with specific examination of the impact of growth hormone deficiency, central hypogonadism, central hypocortisolism, and central hypothyroidism. Pathogenesis, diagnosis, and treatment options as well as challenges posed by osteopenia, osteoporosis, and fractures in hypopituitarism are discussed.

Vascular function and skeletal fragility: A study of tonometry, brachial hemodynamics, and bone microarchitecture.

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these two common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by high-resolution peripheral quantitative computed tomography (HR-pQCT), in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: -0.21 [-0.26,-0.15] standardized beta [95% confidence interval], radius: -0.20 [-0.26,-0.15]), lower cortical thickness (tibia: -0.09 [-0.15,-0.04], radius: -0.07 [-0.12,-0.01]) and increased cortical porosity (tibia: 0.20 [0.15,0.25], radius: 0.21 [0.15,0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health.

BCM-7: Opioid-like Peptide with Potential Role in Disease Mechanisms.

Bovine milk is an essential supplement due to its rich energy- and nutrient-rich qualities. Caseins constitute the vast majority of the proteins in milk. Among these, β-casein comprises around 37% of all caseins, and it is an important type of casein with several different variants. The A1 and A2 variants of β-casein are the most researched genotypes due to the changes in their composition. It is accepted that the A2 variant is ancestral, while a point mutation in the 67th amino acid created the A1 variant. The digestion derived of both A1 and A2 milk is BCM-7. Digestion of A2 milk in the human intestine also forms BCM-9 peptide molecule. The opioid-like characteristics of BCM-7 are highlighted for their potential triggering effect on several diseases. Most research has been focused on gastrointestinal-related diseases; however other metabolic and nervous system-based diseases are also potentially triggered. By manipulating the mechanisms of these diseases, BCM-7 can induce certain situations, such as conformational changes, reduction in protein activity, and the creation of undesired activity in the biological system. Furthermore, the genotype of casein can also play a role in bone health, such as altering fracture rates, and calcium contents can change the characteristics of dietary products. The context between opioid molecules and BCM-7 points to a potential triggering mechanism for the central nervous system and other metabolic diseases discussed.

Cross-sectional associations between accelerometer-measured physical activity and hip bone mineral density. The Tromsø study 2015–2016

Cross-sectional associations between accelerometer-measured physical activity and hip bone mineral density. The Tromsø study 2015–2016

Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot monocenter experience

Bone health and skeletal fragility in second- and third-line medical therapies for acromegaly: preliminary results from a pilot monocenter experience

Early puberty and abnormal bone health: a comprehensive review

Early puberty and abnormal bone health: a comprehensive review

Prolactin impact on aging bone health

Prolactin impact on aging bone health

Long-term bone health in women with a premenopausal risk-reducing salpingo-oophorectomy (RRSO) compared with women who underwent

Long-term bone health in women with a premenopausal risk-reducing salpingo-oophorectomy (RRSO) compared with women who underwent