Healthy lifestyles are associated with better vitamin D status in community-dwelling older men: The Health In Men Study (HIMS).

Objective: Older people are more prone to vitamin D deficiency than younger populations. Individual lifestyle factors have been associated with vitamin D status. We examined the influence of a combination of lifestyle factors on vitamin D status in older men.

Undercarboxylated osteocalcin and ibandronate combination ameliorates hindlimb immobilization-induced muscle wasting.

Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect muscle wasting independent of ucOC.

Rescue of High Glucose Impairment of Cultured Human Osteoblasts Using Cinacalcet and Parathyroid Hormone.

Patients with type 2 diabetes mellitus (T2DM) experience a higher risk of fractures despite paradoxically exhibiting normal to high bone mineral density (BMD). This has drawn into question the applicability to T2DM of conventional fracture reduction treatments that aim to retain BMD. In a primary human osteoblast culture system, high glucose levels (25 mM) impaired cell proliferation and matrix mineralization compared to physiological glucose levels (5 mM).

Vitamin D and Skeletal Muscle: Current Concepts From Preclinical Studies.

Muscle weakness has been recognized as a hallmark feature of vitamin D deficiency for many years. Until recently, the direct biomolecular effects of vitamin D on skeletal muscle have been unclear. Although in the past, some reservations have been raised regarding the expression of the vitamin D receptor in muscle tissue, this special issue review article outlines the clear evidence from preclinical studies for not only the expression of the receptor in muscle but also the roles of vitamin D activity in muscle development, mass, and strength.

Osteoglycin Across the Adult Lifespan.

Context: Osteoglycin (OGN) is a proteoglycan released from bone and muscle which has been associated with markers of metabolic health. However, it is not clear whether the levels of circulating OGN change throughout the adult lifespan or if they are associated with clinical metabolic markers or fitness.

Objective: We aimed to identify the levels of circulating OGN across the lifespan and to further explore the relationship between OGN and aerobic capacity as well as OGN's association with glucose and HOMA-IR.

Adipose Tissue Dysfunction: Impact on Bone and Osseointegration.

Bone metabolism may be adversely affected in metabolic diseases such as obesity and metabolic syndrome, which are characterised by weight gain, due to the expansion of adipose tissue deposits. As an important regulator of energy metabolism, adipose tissues synthesise and secrete several key regulatory adipokines that influence a range of metabolic functions. This narrative review outlines the evidence for the mechanisms by which adipose tissue dysfunction may alter bone metabolism prior to the development of frank hyperglycaemia and presents the emerging evidence for the impact of diet-induced expansion of adipose tissue on implant osseointegration.

Nutritional intake and bone health.

Osteoporotic or fragility fractures affect one in two women and one in five men who are older than 50. These events are associated with substantial morbidity, increased mortality, and an impaired quality of life. Recommended general measures for fragility fracture prevention include a balanced diet with an optimal protein and calcium intake and vitamin D sufficiency, together with regular weight-bearing physical exercise.

The mTORC2 Regulator Homer1 Modulates Protein Levels and Sub-Cellular Localization of the CaSR in Osteoblast-Lineage Cells.

We recently found that, in human osteoblasts, Homer1 complexes to Calcium-sensing receptor (CaSR) and mediates AKT initiation via mechanistic target of rapamycin complex (mTOR) complex 2 (mTORC2) leading to beneficial effects in osteoblasts including β-catenin stabilization and mTOR complex 1 (mTORC1) activation. Herein we further investigated the relationship between Homer1 and CaSR and demonstrate a link between the protein levels of CaSR and Homer1 in human osteoblasts in primary culture. Thus, when siRNA was used to suppress the CaSR, we observed upregulated Homer1 levels, and when siRNA was used to suppress Homer1 we observed downregulated CaSR protein levels using immunofluorescence staining of cultured osteoblasts as well as Western blot analyses of cell protein extracts.

Distinct Effects of a High Fat Diet on Bone in Skeletally Mature and Developing Male C57BL/6J Mice.

Increased risks of skeletal fractures are common in patients with impaired glucose handling and type 2 diabetes mellitus (T2DM). The pathogenesis of skeletal fragility in these patients remains ill-defined as patients present with normal to high bone mineral density. With increasing cases of glucose intolerance and T2DM it is imperative that we develop an accurate rodent model for further investigation.

Associations of Osteocalcin Forms With Metabolic Syndrome and Its Individual Components in Older Men: The Health In Men Study.

Context: The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes.

Objective: We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men.

Uncovering the Bone-Muscle Interaction and Its Implications for the Health and Function of Older Adults (the Wellderly Project): Protocol for a Randomized Controlled Crossover Trial.

Background: Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown.

Is it reasonable to ignore vitamin D status for musculoskeletal health?

Severe vitamin D deficiency-25-hydroxyvitamin D (25OHD) concentrations below around 25-30 nmol/L-may lead to growth plate disorganization and mineralization abnormalities in children (rickets) and mineralization defects throughout the skeleton (osteomalacia) and proximal muscle weakness. Both problems are reversed with vitamin D treatment. Apart from this musculoskeletal dysfunction at very low vitamin D levels, there is apparent inconsistency in the available data about whether concentrations of 25OHD below around 50 nmol/L cause muscle function impairment and increase the risk of fracture.

Higher Undercarboxylated to Total Osteocalcin Ratio Is Associated With Reduced Physical Function and Increased 15-Year Falls-Related Hospitalizations: The Perth Longitudinal Study of Aging Women.

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations.

Association between Circulating Osteocalcin and Cardiometabolic Risk Factors following a 4-Week Leafy Green Vitamin K-Rich Diet.

Background: Evidence suggests that lower serum undercarboxylated osteocalcin (ucOC) may be negatively associated with cardiometabolic health. We investigated whether individuals with a suppression of ucOC following an increase in dietary vitamin K1 exhibit a relative worsening of cardiometabolic risk factors.

Materials And Methods: Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomized, controlled, crossover study.

The effects of acute exercise on bone turnover markers in middle-aged and older adults: A systematic review.

Background: Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs.

Objectives: This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex.

Skeletal Muscle and the Maintenance of Vitamin D Status.

Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation.

Osteocalcin and measures of adiposity: a systematic review and meta-analysis of observational studies.

Unlabelled: Osteocalcin, the osteoblast-derived protein, has been shown to be modulated in patients with problematic glucose metabolism. Our systematic review and meta-analysis found that in humans, higher blood osteocalcin level is associated with lower body indices of fat.

Purpose/introduction: Osteocalcin (OC) was found to be inversely correlated with measures of glucose and energy metabolism, with some groups suggesting the undercarboxylated form (ucOC) to be metabolically active, although the link is not clear, especially in humans.

The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals.

Background: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism.

Multifactorial effects of hyperglycaemia, hyperinsulinemia and inflammation on bone remodelling in type 2 diabetes mellitus.

Bones undergo continuous cycles of bone remodelling that rely on the balance between bone formation and resorption. This balance allows the bone to adapt to changes in mechanical loads and repair microdamages. However, this balance is susceptible to upset in various conditions, leading to impaired bone remodelling and abnormal bones.

Sleep duration is associated with vitamin D deficiency in older women living in Macao, China: A pilot cross-sectional study.

Chinese women are known to have both a high prevalence of metabolic syndrome (MetS) and vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) <50 nmol/l). Associations between sleep duration and circulating 25OHD have recently been reported but, to our knowledge, these associations have not been studied in older Chinese populations. We thus investigated whether sleep duration was associated with vitamin D status in a population from Macao, China, and whether sleep duration modified the association between MetS and vitamin D deficiency.

A diet high in fat and fructose adversely affects osseointegration of titanium implants in rats.

Objectives: Diet-induced metabolic dysfunction such as type 2 diabetes mellitus increases the risk of implant failure in both dental and orthopaedic settings. We hypothesised that a diet high in fat and fructose would adversely affect peri-implant bone structure and function including osseointegration.

Materials And Methods: Thirty female Sprague-Dawley rats were divided into three groups (n = 10), control group (normal chow) and two intervention groups on a high-fat (60%), high-fructose (20%; HFHF) diet.

Effects of Vitamin D Status and Supplements on Anthropometric and Biochemical Indices in a Clinical Setting: A Retrospective Study.

Context: Obesity and low vitamin D status are linked. It is not clear that weight loss through lifestyle intervention is influenced by vitamin D status.

Objective: The aim of this study was to investigate the effect of baseline vitamin D status and vitamin D supplementation on weight loss and associated parameters for participants on a weight loss program in a primary care setting.

Osteocalcin and its forms across the lifespan in adult men.

Purpose: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease.

The Role of Skeletal Muscle in Maintaining Vitamin D Status in Winter.

The status of vitamin D is determined mainly by its formation in skin by the photochemical action of solar UVB light (wavelength 290-320 nm) on the precursor 7-dehydrocholesterol. Because of seasonal variation in intensity of solar UV light, vitamin D status falls in winter and rises in summer. It has been presumed that there is no functional store of vitamin D.

Homer1 mediates CaSR-dependent activation of mTOR complex 2 and initiates a novel pathway for AKT-dependent β-catenin stabilization in osteoblasts.

The calcium-sensing receptor (CaSR) is critical for skeletal development, but its mechanism of action in osteoblasts is not well-characterized. In the central nervous system (CNS), Homer scaffolding proteins form signaling complexes with two CaSR-related members of the G protein-coupled receptor (GPCR) family C, metabotropic glutamate receptor 1 (mGluR1) and mGluR5. Here, we show that CaSR and Homer1 are co-expressed in mineralized mouse bone and also co-localize in primary human osteoblasts.