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Vitamin D and K are believed to promote bone health, but existing evidence is controversial. This study aimed to measure several metabolites of both vitamins by liquid chromatography tandem mass spectrometry (LC-MS/MS) in a cohort of postmenopausal women with low and normal bone mineral density (BMD). Vitamin metabolites (25-hydroxyvitamin D (25[OH]D), 24,25-dihydroxyvitamin D (24,25(OH)2D), phylloquinone (K1), menaquinone-4 (MK-4) and MK-7) were measured in 131 serum samples by LC-MS/MS. The vitamin D metabolite ratio (VMR) was calculated. Parathyroid hormone (PTH), type I procollagen-N-terminal-peptide (PINP) and C-terminal telopeptides of type I collagen (CTX-I) were measured by immunoassay. Dual X-ray absorptiometry was performed to identify participants with normal (T-score>−1) and low (T-score<−1) BMD. Mean age was 58.2±8.5 years. BMD was normal in 68 and low in 63 women. Median (interquartile range) for 25(OH)D and total vitamin K concentrations were 53.5 (39.6–65.9) nmol/L and 1.33 (0.99–2.39) nmol/L. All vitamin metabolites were comparable in individuals with normal and low BMD. Furthermore, BMD and trabecular bone score were comparable in participants with adequate and inadequate vitamin status (at least one criterion was met: 25(OH)D <50 nmol/L, 24,25(OH)2D <3 nmol/L, VMR <4 %, total vitamin K <0.91 nmol/L). PTH, but not PINP or CTX-I, was inversely correlated with 25(OH)D, 24,25(OH)2D and VMR. Synergistic effects between vitamin D and K were not observed. Vitamin D and K status is not related to BMD and trabecular bone quality in postmenopausal women. Inverse associations were only seen between vitamin D metabolites and PTH. [ABSTRACT FROM AUTHOR]

Objective: As our society grows older, both bone loss and fatty liver have become important issues. However, the relationship between reduced bone mineral density and fatty liver remains controversial. The purpose of this study was to investigate the relationship between nonalcoholic fatty liver disease and less bone mineral density in the ankles of Chinese people over 65. Methods: The research included 716 older adults over the age of 65 who underwent a comprehensive health screening. A logistic regression model was used to investigate the relationship between nonalcoholic fatty liver disease (NAFLD) and ankle bone mineral density. Results: A logistic regression model was used to analyze the odds ratios of reduced bone mineral density between patients with fatty liver and controls. In the adjusted model, adjustments were made for age, sex, systolic blood pressure, diastolic blood pressure, overweight rate, history of hypertension, history of diabetes, history of smoking, history of alcohol consumption, fasting glucose, hemoglobin, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, waist circumference, total protein, albumin, and globulin. The adjusted OR (aOR) for reduced bone mineral density was 0.66 [95% confidence interval (CI) = 0.45–0.97, P = 0.034 < 0.05]. In subgroup analysis by age, sex, and BMI, women, age > 75 years, and BIM < 25 were statistically significant. Conclusion: This study suggested that NAFLD is associated with a reduced risk of reduced heel bone mass. More research needs to be done to back up the results of this study and look into possible problems. [ABSTRACT FROM AUTHOR]

Mounting evidence has supported osteoporosis (OP) as a metabolic disorder. Recent metabolomics studies have discovered numerous metabolites related to bone mineral density (BMD). However, the causal effects of metabolites on BMD at distinct sites remained underexplored. Leveraging genome-wide association datasets, we conducted two-sample Mendelian randomization (MR) analyses to investigate the causal relationship between 486 blood metabolites and bone mineral density at five skeletal sites including heel (H), total body (TB), lumbar spine (LS), femoral neck (FN), and ultra-distal forearm (FA). Sensitivity analyses were performed to test the presence of the heterogeneity and the pleiotropy. To exclude the influences of reverse causation, genetic correlation, and linkage disequilibrium (LD), we further performed reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses. In the primary MR analyses, 22, 10, 3, 7, and 2 metabolite associations were established respectively for H-BMD, TB-BMD, LS-BMD, FN-BMD, and FA-BMD at the nominal significance level (IVW, P < 0.05) and passing sensitivity analyses. Among these, one metabolite, androsterone sulfate showed a strong effect on four out of five BMD phenotypes (Odds ratio [OR] for H-BMD = 1.045 [1.020, 1.071]; Odds ratio [OR] for TB-BMD = 1.061 [1.017, 1.107]; Odds ratio [OR] for LS-BMD = 1.088 [1.023, 1.159]; Odds ratio [OR] for FN-BMD = 1.114 [1.054, 1.177]). Reverse MR analysis provided no evidence for the causal effects of BMD measurements on these metabolites. Colocalization analysis have found that several metabolite associations might be driven by shared genetic variants such as mannose for TB-BMD. This study identified some metabolites causally related to BMD at distinct sites and several key metabolic pathways, which shed light on predictive biomarkers and drug targets for OP. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis (OP) is a debilitating disease that brings a heavy burden to individuals and society with reduced quality of life and lifespan. However, it's frequently overlooked and poorly studied in elderly male patients. Worse still, few anti-osteoporosis drugs are effective at the prevention and treatment of osteoporosis in men. It has been reported that the cells of bone and the immune system share common progenitors, cytokines and growth factors, and that reciprocal interactions occur during health and disease. Nevertheless, the role of immune system in OP is not fully understood, especially in male patients. Therefore, this study aimed to investigate molecular alterations in immune cells in men with OP and to identify immunomodulatory strategies with potential therapeutic value. Materials and Methods: A population of 121 men aged between 51 and 80 years old was recruited. Bone mineral density (BMD) was measured at the lumbar spine L1-4 and femoral neck using dual-energy X-ray absorptiometry (DXA). Twenty people were healthy, 66 people had osteopenia and 35 people had OP. Bone metabolic markers, Th1, Th2, Tregs and immune molecules were evaluated at the time of enrollment. Results: Smoking was a risk factor for OP. C-terminal crosslinking of type I collagen (β-CTX) and the ratio of receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) were higher in OP group, which had lower 25-hydroxyvitamin D [25(OH)D] levels. OP had the higher levels of IL-6 and TNF-α and lower levels of IFN-γ and IL-10. CD4+CD25+CD127-/low Tregs were significantly lower in the OP group. The imbalance of Th1/Th2 cells may play an important role in the development of OP. 25(OH)D may play essential roles in maintaining bone health. The low level of Tregs is also one of the underlying immune mechanism that leads to male primary OP. Conclusion: The active function of osteoclasts and the decline in osteoblasts were characteristics of OP, and the imbalance in cytokines and lower levels of Tregs were observed in elderly male patients with primary OP. [ABSTRACT FROM AUTHOR]

Background: With the increasing incidence of osteoporosis, vitamin K and calcium have been linked to bone mineral density (BMD) and undercarboxylated osteocalcin (UcOC) in many studies, but the results of studies of the combined effect of vitamin K and calcium on BMD and UcOC in humans have been inconsistent. We conducted a systematic review of randomized controlled trials to assess the effect of this combination treatment on BMD and UcOC in humans. Methods: A search for articles was conducted using PubMed, Embase, and the Cochrane Library database up to March 2021 (no language restrictions). We also reviewed the reference lists of the relevant publications and reviews to locate additional publications. The standard mean difference (SMD) was used as the primary measure of effect size. Our main endpoints were lumbar BMD, femoral neck BMD, hip BMD, total femoral BMD, and UcOC from baseline to end point. We performed subgroup analysis, heterogeneity testing, and assessment of publication bias. Results: A total of 1346 patients from 10 randomized controlled trials were included in the meta-analysis. The forest plot analysis revealed that vitamin K combined with calcium was associated with a higher lumbar spine BMD compared to controls. The SMD was 0.20 [95% confidence interval (CI): 0.07 to 0.32]. Vitamin K and calcium supplementation led to a significant decrease in UcOC (SMD: − 1.71, 95% CI: − 2.45 to − 0.96). Subgroup analysis showed that vitamin K2 and vitamin K1 had SMDs of 0.30 (95% CI: 0.10 to 0.51) and SMDs of 0.14 (95% CI: − 0.02 to 0.29), and calcium dosages of ≤ 1000 mg/d or > 1000 mg/d had SMDs of 0.19 (95% CI: 0.05 to 0.32) and 0.26 (95% CI: − 0.04 to 0.55). Conclusion: The combination of vitamin K and calcium has a positive effect on lumbar BMD and decreases the level of UcOC. Registration: The protocol for this meta-analysis was registered at the International Prospective Register of Systematic Reviews (CRD42021251825). [ABSTRACT FROM AUTHOR]

Summary: In recent years, a growing interest on the impact of statin intake on bone health has emerged, although the reported results are controversial. The results of this study revealed that BMD at lumbar spine has a significant association with statin intake. However, such association appears to be weaker regarding TBS values compared to BMD. This study was performed with the aim of evaluating associations of statin intake with BMD and TBS using data from 2426 individuals aged ≥ 60 years from the second phase of the Bushehr Elderly Health (BEH) program. We found a positive association between statin and BMD at lumbar spine, whereas association between statin and TBS was detected only in the men in the final model. Introduction: In recent years, a growing interest has been established to evaluate the impact of statin intake on bone health, although the reported results are controversial. This study aimed to evaluate the association of statin intake with bone health status according to BMD and TBS. Methods: This cross-sectional analysis used data from the elderly Iranian individuals who participated in the Bushehr Elderly Health (BEH) program. Dual x-ray absorptiometry (DXA) device was used to evaluate the BMD at lumbar spine (L1–L4), femoral neck, and total hip, as well as TBS at lumbar spine. Results: Among 2426 (1260 women and 1166 men) study participants, 778 were statin users. A positive significant association, irrespective of sex, was observed between statin intake and BMD at L1–L4, even after controlling for potential variables in total population (β = 0.016, p = 0.013). The mean TBS values at L1–L4 were negatively associated with statin intake in total population (β = − 0.009, p = 0.001), while in the full adjusted model, significant positive association between TBS and statin intake was detected only in men (β = 0.013, p = 0.02). Conclusion: The results of this study revealed that BMD at lumbar spine has a significant association with statin intake. However, such an association appears to be weaker regarding TBS values compared to BMD. [ABSTRACT FROM AUTHOR]

Summary: We evaluated the association of bone fracture with mortality among persons with HIV, controlling for sociodemographic, behavioral, and clinical factors. Incident fracture was associated with 48% greater risk of all-cause mortality, underscoring the need for bone mineral density screening and fracture prevention. Purpose/Introduction: Low bone mineral density (BMD) and fracture are more common among persons with HIV (PWH) than those without HIV infection. We evaluated the association of bone fracture with mortality among PWH, controlling for sociodemographic, behavioral, and clinical factors. Methods: We analyzed data from HIV Outpatient Study (HOPS) participants seen at nine US HIV clinics during January 1, 2000, through September 30, 2017. Incident fracture rates and post-fracture mortality were compared across four calendar periods. Cox proportional hazards analyses determined factors associated with all-cause mortality among all participants and those with incident fracture. Results: Among 6763 HOPS participants, 504 (7.5%) had incident fracture (median age = 47 years) and 719 (10.6%) died. Of fractures, 135 (26.8%) were major osteoporotic (hip/pelvis, wrist, spine, arm/shoulder). During observation, 27 participants with major osteoporotic fractures died (crude mortality 2.97/100 person-years [PY]), and 48 with other site fractures died (crude mortality 2.51/100 PY). Post-fracture, age- and sex-adjusted all-cause mortality rates per 100 PY decreased from 8.5 during 2000–2004 to 1.9 during 2013–2017 (P<0.001 for trend). In multivariable analysis, incident fracture was significantly associated with all-cause mortality (Hazard Ratio 1.48, 95% confidence interval 1.15–1.91). Among 504 participants followed post-fracture, pulmonary, kidney, and cardiovascular disease, hepatitis C virus co-infection, and non-AIDS cancer, remained independently associated with all-cause mortality. Conclusions: Incident fracture was associated with 48% greater risk of all-cause mortality among US PWH in care, underscoring the need for BMD screening and fracture prevention. Although fracture rates among PWH increased during follow-up, post-fracture death rates decreased, likely reflecting advances in HIV care. [ABSTRACT FROM AUTHOR]

Introduction: In chronic hemodialysis, high-turnover bone disease was associated with decreased bone mineral density (BMD), poor bone quality (chemical and structural), and increased fracture risk. Our aim was to correlate bone turnover markers (BTMs) with bone microarchitecture measured by trabecular bone score (TBS) before and after correction for BMD.Materials and Methods: We measured lumbar spine (LS), femoral neck, and 1/3 radius BMD and LS TBS by dual X-ray absorptiometry in 81 patients on permanent hemodialysis. Bone turnover was assessed using serum parathyroid hormone, osteocalcin, C-terminal crosslaps of type 1 collagen, procollagen 1 N-terminal propeptide (P1NP), and alkaline phosphatase (ALP). No patient had any partial or total parathyroidectomy and no previous or current treatment with anti-osteoporotic drugs.Results: All BTMs correlated significantly with each other. Univariate regressions showed significant negative correlations between BTMs and BMD (best r = - 0.53, between P1NP and 1/3 radius Z-score) or BTMs and TBS (best r = - 0.27, p < 0.05 between ALP and TBS T-score). TBS correlated significantly with BMD at all three sites (best r = 0.5, between LS BMD and TBS T-score). Multivariate regression showed that TBS, crude or adjusted, correlated with LS BMD. No model retained any of the BTMs as independent variables due to the better prediction of BMD and multicollinearity.Conclusion: We showed a progressively impaired bone microarchitecture with increasing bone turnover in chronic hemodialysis. However, this correlation is no longer present when controlling for bone mass. This suggests that impaired bone microarchitecture and increased fracture risk are dependent upon factors other than high bone turnover. [ABSTRACT FROM AUTHOR]

Purpose: Fish is a source of various nutrients beneficial for bone health, but few studies have investigated the association between bone mineral density (BMD) and fish consumption. Thus, the aim was to investigate the relationship between total fish intake and BMD and between both lean and fatty fish intake and BMD. Method: These cross-sectional analyses include 4656 participants in the Hordaland Health Study, a community-based study conducted in 1997–1999. The study includes two birth cohorts of men and women from Hordaland county (Norway) born in 1950–1951 and 1925–1927. BMD was measured by dual-energy X-ray absorptiometry and dietary intake was obtained from a semi-quantitative food-frequency questionnaire. Results: The average total fish intake was 33 ± 18 g/1000 kcal and was primarily lean fish. Older women had significantly lower BMD than older men and middle-aged men and women. In older women, total and lean fish intake (50 g/1000 kcal) was significantly and positively associated with BMD also after multivariate adjustments (β-coefficient 0.018, p = 0.017 and 0.026, p = 0.021). Conclusion: A high intake of fish, in particular lean fish, was positively associated with BMD in older women. No association between intake of fatty fish and BMD was found in either of the age and sex groups. [ABSTRACT FROM AUTHOR]

Background: Smoking has deleterious effects on bone mass and is associated with the subsequent development of osteoporosis, particularly in elderly participants. The purpose of this study was to determine the influence of smoking in the elderly male smokers. Methods: All male participants aged 60 years and older of the Amirkola cohort who performed bone densitometry entered the study. Bone mineral density (BMD) was measured at the lumbar spine (LS) and femoral neck (FN) using the dual-energy X-ray absorptiometry method. In statistical analysis, the smokers and nonsmokers were compared according to BMD, frequency of low bone mass defined as BMD T-score <-1 at either LS or FN, and the number of bone fractures. SPSS software version 18 was used for analysis. Results: A total of 203 smokers with mean smoking duration of 21.67 ± 17.7 years and the mean number of 36.4 + 15.8 cigarettes per day were compared with 408 nonsmokers. The mean BMD values in LS (0.90 ± 0.14 vs. 0.94 ± 0.19) and FN section (0.87 ± 0.13 vs. 0.89 ± 0.15) and also the frequency of bone fractures were significantly lower, and the frequency of low bone mass at either LS and FN was significantly higher in smokers (P = 0.014, 0.038, 0.003, and 0.004, respectively). In multiple logistic regression analysis, smoking was independently associated with low bone mass by odds ratio of = 2.27 (95% confidence interval: 1.49-3.44). Conclusions: These findings indicate a significant association between low bone mass and bone fracture at either LS or FN in the elderly male smokers. [ABSTRACT FROM AUTHOR]

Distal radius fracture is an early indicator of osteoporosis, yet little is known about men with this fracture and osteoporosis prevalence. The purpose of this cross-sectional, controlled study was to evaluate bone mineral density (BMD) in men, from working age to the elderly, with distal radius fracture. Recruitment was as follows: men who fractured during 1999-2000 were evaluated retrospectively in 2003 and men who fractured during 2003-2007 were followed prospectively for one year post-fracture. A total of 233 patients, response rate 40 %, were enrolled and compared with 643 controls. Fractures from all degrees of trauma were included. BMD was measured at femoral neck, total hip, and lumbar spine. Mean age at fracture was 52 years (21-88 years). Men aged 40-64 years had 5.4-6.7 % lower BMD at all sites compared to controls (p = 0.001) and in >65 years BMD was lower by 10.7-13.8 % (p < 0.001), while not significant at <40 years (1.4-2.8 %; p = 0.228-0.487). Osteoporosis was more prevalent at all ages (20-39 years: 8.5 vs 1.5 %; 40-64 years: 16.8 vs 5.1 %; >65 years: 23.3 vs 8.3 %) BMD did not differ with trauma level. Already from age 40, men with a distal radius fracture had lower BMD, the difference becoming more pronounced with increasing age. Also, the prevalence of osteoporosis was higher, surprisingly even in the youngest age group. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the effects of chronic sleep deprivation (CSD) on bone mass and bone metabolism in rats. Methods: Twenty-four rats were randomly divided into CSD and control (CON) groups. Rats were subjected to CSD by using the modified multiple platform method (MMPM) to establish an animal model of CSD. Biochemical parameters such as levels of serum N-terminal propeptide of type I procollagen (PINP), N-terminal cross-linking telopeptide of type I collagen (NTX), growth hormone (GH), estradiol (E2), serum 25(OH)D, and calcium (Ca) were evaluated at 0, 1, 2, and 3 months. After 3 months, each fourth lumbar vertebra and the distal femoral metaphysis of the left extremity of rats were harvested for micro-computed tomography scans and histological analysis, respectively, after the rats were sacrificed under an overdose of pentobarbital sodium. Results: Compared with rats from the CON group, rats from the CSD group showed significant decreases in bone mineral density (BMD), bone volume over total volume, trabecular bone thickness, and trabecular bone number and significant increases in bone surface area over bone volume and trabecular bone separations (P<0.05). Bone histomorphology studies showed that rats in the CSD group had decreased osteogenesis, impaired mineralization of newly formed bones, and deteriorative trabecular bone in the secondary spongiosa zone. In addition, they showed significantly decreased levels of serum PINP (1 month later) and NTX (3 months later) (P < 0.05). The serum 25(OH)D level of rats from the CSD group was lower than that of rats from the CON group after 1 month (P < 0.05). Conclusions: CSD markedly affects bone health by decreasing BMD and 25(OH)D, deteriorating the bone microarchitecture, and decreasing bone formation and bone resorption markers. [ABSTRACT FROM AUTHOR]

Summary: In the large community-based Hordaland Health Study, low plasma dimethylglycine was associated with low bone mineral density in both middle-aged and elderly subjects and to an increased risk of subsequent hip fracture among the elderly. These associations seemed to be particularly strong among subjects exposed to nicotine. Introduction: Dimethylglycine (DMG) is a product of the choline oxidation pathway and formed from betaine during the folate-independent remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are associated with atherosclerotic cardiovascular disease and inflammation, which in turn are related to osteoporosis. High plasma total Hcy and low plasma choline are associated with low bone mineral density (BMD) and hip fractures, but the role of plasma DMG in bone health is unknown. Methods: We studied the associations of plasma DMG with BMD among 5315 participants (46-49 and 71-74 years old) and with hip fracture among 3310 participants (71-74 years old) enrolled in the Hordaland Health Study. Results: In age and sex-adjusted logistic regression models, subjects in the lowest versus highest DMG tertile were more likely to have low BMD (odds ratio [OR] 1.68, 95 % confidence interval [CI] 1.43-1.99). The association was stronger in participants exposed compared to those unexposed to nicotine (OR 2.31, 95 % CI 1.73-3.07 and OR 1.43, 95 % CI 1.16-1.75, respectively, p interaction = 0.008). In the older cohort, Cox regression analyses adjusted for sex showed that low plasma DMG was associated with an increased risk of hip fracture (hazard ratio [HR] 1.70, 95 % CI 1.28-2.26). A trend toward an even higher risk was found among women exposed to nicotine (HR 3.41, 95 % CI 1.40-8.28). Conclusion: Low plasma DMG was associated with low BMD and increased risk of hip fractures. A potential effect modification by nicotine exposure merits particular attention. [ABSTRACT FROM AUTHOR]

Patients with chronic liver diseases frequently exhibit decreased bone mineral densities (BMD), which is defined as hepatic osteodystrophy (HOD). HOD is a multifactorial disease whose regulatory mechanisms are barely understood. Thus, an early diagnosis and therapy is hardly possible. Therefore, the aim of our study consisted in characterizing a mouse model reflecting the human pathomechanism. Serum samples were collected from patients with chronic liver diseases and 12-week old C57Bl6/N mice after 6-week treatment with carbon tetrachloride (CCl). Repetitive injections of CCl induced liver damage in mice, resembling liver fibrosis in patients, as assessed by serum analysis and histological staining. Although CCl did not affect primary osteoblast cultures, μCT analysis revealed significantly decreased BMD, bone volume, trabecular number and thickness in CCl-treated mice. In both HOD patients and CCl-treated mice, an altered vitamin D metabolism with decreased CYP27A1, CYP2R1, vitamin D-binding protein GC and increased 7-dehydrocholesterol reductase hepatic gene expression, results in decreased 25-OH vitamin D serum levels. Moreover, both groups exhibit excessively high active transforming growth factor-beta (TGF-β) serum levels, inhibiting osteoblast function in vitro. Summarizing, our mouse model presents possible mediators of HOD, e.g. altered vitamin D metabolism and increased active TGF-β. Liver damage and significant changes in bone structure and mineralization are already visible by μCT analysis after 6 weeks of CCl treatment. This fast response and easy transferability makes it an ideal model to investigate specific gene functions in HOD. [ABSTRACT FROM AUTHOR]

Summary: We have investigated whether low-dose vitamin K2 supplements (menaquinone-7, MK-7) could beneficially affect bone health. Next to an improved vitamin K status, MK-7 supplementation significantly decreased the age-related decline in bone mineral density and bone strength. Low-dose MK-7 supplements may therefore help postmenopausal women prevent bone loss. Introduction: Despite contradictory data on vitamin K supplementation and bone health, the European Food Safety Authorities (EFSA) accepted the health claim on vitamin K's role in maintenance of normal bone. In line with EFSA's opinion, we showed that 3-year high-dose vitamin K1 (phylloquinone) and K2 (short-chain menaquinone-4) supplementation improved bone health after menopause. Because of the longer half-life and greater potency of the long-chain MK-7, we have extended these investigations by measuring the effect of low-dose MK-7 supplementation on bone health. Methods: Healthy postmenopausal women ( n = 244) received for 3 years placebo or MK-7 (180 μg MK-7/day) capsules. Bone mineral density of lumbar spine, total hip, and femoral neck was measured by DXA; bone strength indices of the femoral neck were calculated. Vertebral fracture assessment was performed by DXA and used as measure for vertebral fractures. Circulating uncarboxylated osteocalcin (ucOC) and carboxylated OC (cOC) were measured; the ucOC/cOC ratio served as marker of vitamin K status. Measurements occurred at baseline and after 1, 2, and 3 years of treatment. Results: MK-7 intake significantly improved vitamin K status and decreased the age-related decline in BMC and BMD at the lumbar spine and femoral neck, but not at the total hip. Bone strength was also favorably affected by MK-7. MK-7 significantly decreased the loss in vertebral height of the lower thoracic region at the mid-site of the vertebrae. Conclusions: MK-7 supplements may help postmenopausal women to prevent bone loss. Whether these results can be extrapolated to other populations, e.g., children and men, needs further investigation. [ABSTRACT FROM AUTHOR]