Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients.

Breast cancer is a significant public health issue affecting women worldwide. While advancements in treatment options have led to improved survival rates, the impact of breast cancer and its treatments on bone health cannot be overlooked. Bone remodeling is a complex process regulated by the delicate balance between bone formation and resorption. Any disruption to this balance can lead to decreased bone density, increased fracture risk, and compromised physical function. To investigate the effects of breast cancer and its treatments on bone remodeling, a finite element model was developed in this study. This model incorporated bone remodeling equations to simulate the mechanical behavior of bone under different conditions. The ABAQUS/UMAT software was used to simulate the behavior of bone tissue under the influence of breast cancer and treatments. Our findings suggest that bone loss is more pronounced after secondary breast cancer and treatment, leading to bone loss (6%-19% decrease in BV/TV), reduced bone stimulation, and decreased effectiveness of physical activity on recovery. These results highlight the importance of early intervention and management of bone health in breast cancer patients to mitigate the negative impact of cancer and treatment on bone remodeling.

The use of alkaline phosphatase as a bone turnover marker after spinal cord injury: A scoping review of human and animal studies.

BACKGROUND: Serum alkaline phosphatase (ALP) is measured as an indicator of bone or liver disease. Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in the bone tissue which can predict fractures and heterotopic ossification. OBJECTIVE: The aim of this scoping review was to explore the current use of ALP and B-ALP in studies using humans or animal models of SCI, and to identify ways to advance future research using ALP and B-ALP as a bone marker after SCI. RESULTS: HUMAN STUDIES: 42 studies were included. The evidence regarding changes or differences in ALP levels in individuals with SCI compared to controls is conflicting. For example, a negative correlation between B-ALP and total femur BMD was observed in only one of three studies examining the association. B-ALP seemed to increase after administration of teriparatide, and to decrease after treatment with denosumab. The effects of exercise on ALP and B-ALP levels are heterogeneous and depend on the type of exercise performed. ANIMAL STUDIES: 11 studies were included. There is uncertainty regarding the response of ALP or B-ALP levels after SCI; levels increased after some interventions, including vibration protocols, curcumin supplementation, cycles in electromagnetic field or hyperbaric chamber. Calcitonin or bisphosphonate administration did not affect ALP levels. CONCLUSION: Researchers are encouraged to measure the bone-specific isoform of ALP rather than total ALP in future studies in humans of animal models of SCI.

Hyperbaric oxygen therapy improves age induced bone dyshomeostasis in non-obese and obese conditions.

AIMS: To investigate the effects of hyperbaric oxygen therapy (HBOT) on metabolic disturbance, aging and bone remodeling in D-galactose-induced aging rats with and without obesity by determining the metabolic parameters, aging and oxidative stress markers, bone turnover markers, bone microarchitecture, and bone biomechanical strength. MATERIALS AND METHODS: Male Wistar rats were fed either a normal diet (ND; n = 18) or a HFD (n = 12) for 22 weeks. At week 13, vehicle (0.9% NaCl) was injected into ND-fed rats (NDV; n = 6), while 150 mg/kg/day of D-galactose was injected into 12 ND-fed rats (NDD) and 12 HFD-fed rats (HFDD) for 10 weeks. At week 21, rats were treated with either sham (NDVS, NDDS, or HFDDS; n = 6/ group) or HBOT (NDDH, or HFDDH; n = 6/group) for 14 days. Rats were then euthanized. Blood samples, femora, and tibiae were collected. KEY FINDINGS: Both NDD and HFDD groups developed aging as indicated by increased AGE level, increased inflammation and oxidative stress as shown by raised serum TNF-α and MDA levels, impaired bone remodeling as indicated by an increase in levels of CTX-1, TRACP-5b, and impaired bone structure/strength, when compared with those of the NDVS group. HFD aggravated these indicators of bone dyshomeostasis in D-galactose-treated rats. HBOT restored bone remodeling and bone structure/strength in the NDD group, however HBOT ameliorated bone dyshomeostasis in the HFDD group. SIGNIFICANCE: HBOT is a potential intervention to decrease the risk of osteoporosis and bone fracture in aging with or without obesity.

The Effect of Caloric Restriction with and without n-3 PUFA Supplementation on Bone Turnover Markers in Blood of Subjects with Abdominal Obesity: A Randomized Placebo-Controlled Trial.

Weight loss contributes to an increased risk of hip fracture, especially in postmenopausal women. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation could diminish the adverse effect of weight loss on bone health. The aim of this randomized, placebo-controlled, double-blind parallel trial was to investigate the effect of caloric restriction and n-3 PUFA supplement intake on osteogenic markers (carboxylated osteocalcin (Gla-OC); procollagen I N-terminal propeptide (PINP)), as well as a bone resorption marker (C-terminal telopeptide of type I collagen (CTX-I)) in a serum of 64 middle aged individuals (BMI 25-40 kg/m2) with abdominal obesity. Bone remodeling, metabolic and inflammatory parameters and adipokines were determined before and after 3 months of an isocaloric diet (2300-2400 kcal/day) or a low-calorie diet (1200 kcal/day for women and 1500 kcal/day for men) along with n-3 PUFA (1.8 g/day) or placebo capsules. CTX-I and adiponectin concentrations were increased following 7% weight loss independently of supplement use. Changes in CTX-I were positively associated with changes in adiponectin level (rho = 0.25, p = 0.043). Thus, an increase in serum adiponectin caused by body weight loss could adversely affect bone health. N-3 PUFAs were without effect.

Efficacy of Creatine Supplementation and Resistance Training on Area and Density of Bone and Muscle in Older Adults.

PURPOSE: To examine the efficacy of creatine (Cr) supplementation and any sex differences during supervised whole-body resistance training (RT) on properties of bone and muscle in older adults. METHODS: Seventy participants (39 men, 31 women; mean age ± standard deviation: 58 ± 6 yr) were randomized to supplement with Cr (0.1 g·kg-1·d-1) or placebo (Pl) during RT (3 d·wk-1 for 1 yr). Bone geometry (radius and tibia) and muscle area and density (forearm and lower leg) were assessed using peripheral quantitative computed tomography. RESULTS: Compared with Pl, Cr increased or maintained total bone area in the distal tibia (Cr, Δ +17 ± 27 mm2; Pl, Δ -1 ± 22 mm2; P = 0.031) and tibial shaft (Cr, Δ 0 ± 9 mm2; Pl, Δ -5 ± 7 mm2; P = 0.032). Men on Cr increased trabecular (Δ +28 ± 31 mm2; P < 0.001) and cortical bone areas in the tibia (Δ +4 ± 4 mm2; P < 0.05), whereas men on Pl increased trabecular bone density (Δ +2 ± 2 mg·cm-3; P < 0.01). There were no bone changes in the radius (P > 0.05). Cr increased lower leg muscle density (Δ +0.83 ± 1.15 mg·cm-3; P = 0.016) compared with Pl (Δ -0.16 ± 1.56 mg·cm-3), with no changes in the forearm muscle. CONCLUSIONS: One year of Cr supplementation and RT had some favorable effects on measures of bone area and muscle density in older adults.

Oligopin® Supplementation Mitigates Oxidative Stress in Postmenopausal Women with Osteopenia: A Randomized, Double-blind, Placebo-Controlled Trial.

BACKGROUND: Evidence indicates a close association between oxidative stress and the etiopathogenesis of osteopenia. In vitro and animal studies report that Oligopin®, an extract of French maritime pine bark extract, has beneficial effects on oxidative stress. PURPOSE: Here, we aimed to determine whether supplementation with Oligopin® affects bone turnover markers, antioxidant enzymes, and oxidative stress markers in these patients. METHODS: Forty-three postmenopausal women with osteopenia were randomized in a placebo-controlled, double-blind clinical trial to receive either 150 mg/day Oligopin® (n = 22) or placebo (n = 21) for 12 weeks. Plasma levels of bone turnover markers; osteocalcin (OC), type I collagen cross-linked C-telopeptide (CTX-1), OC/CTX1 ratio along with total antioxidant capacity(TAC), malondialdehyde (MDA) concentration, protein carbonyl, and total thiol contents in plasma, activities of manganese superoxide dismutase (MnSOD) and catalase in both peripheral blood mononuclear cells (PBMCs) and plasma as well as mRNA expression of MnSOD, catalase, and Nrf2 in PBMCs were measured at the baseline and the end of the intervention. RESULTS: Oligopin® supplementation significantly increased OC levels and the ratio of OC to CTX1 in women with osteopenia compared to placebo intervention after 12 weeks. Oligopin® significantly decreased plasma protein carbonyl content in postmenopausal women compared with the after placebo treatment. Moreover, Oligopin® intervention significantly increased plasma total thiol content, TAC, plasma activity of both MnSOD and catalase, and the transcript level of Nrf2, MnSOD, and catalase in comparison with the placebo group. CONCLUSION: Supplementation with 150 mg/day Oligopin® for 12 weeks exerts beneficial effects in postmenopausal osteopenia through improving the antioxidant defense system in the plasma and PBMCs that was accompanied by an increase in indicators of bone turnover.

Selenium: A Trace Element for a Healthy Skeleton - A Narrative Review.

Inadequate serum selenium levels may delay the growth and physiological changes in bone metabolism. In humans, reduced serum selenium concentrations are associated with both increased bone turnover and reduced bone mineral density. Moreover, a reduced nutritional intake of selenium may lead to an increased risk of bone disease. Therefore, selenium is an essential nutrient playing a role in bone health, probably due to specific selenium-proteins. Some selenium-proteins have an antioxidation enzymatic activity and participate in maintaining the redox cellular balance, regulating inflammation and proliferation/differentiation of bone cells too. At least nine selenium-proteins are known to be expressed by fetal osteoblasts and appear to protect bone cells from oxidative stress at bone microenvironment. Mutations of selenium-proteins and reduced circulating levels of selenium are known to be associated with skeletal diseases such as the Kashin-Beck osteoarthropathy and postmenopausal osteoporosis. In addition, the intake of selenium appears to be inversely related to the risk of hip fragility fractures. Recent data suggest that an altered selenium state may affect bone mass even in males and selenium-proteins and selenium concentrations were positively associated with the bone mass at femoral, total and trochanteric sites. However, selenium, but not selenium-proteins, seems to be associated with femoral neck bone mass after adjustment for many bone fracture risk factors. The present review summarizes the findings of observational and interventional studies, which have been designed for investigating the relationship between selenium and bone metabolism.

Therapeutic and Mechanistic Approaches of Tridax Procumbens Flavonoids for the Treatment of Osteoporosis.

Homeostasis of bone is closely regulated by the balanced activities between the bone resorbing activity of osteoclast cells and bone-forming ability of osteoblast cells. Multinucleated osteoclasts degrade bone matrix and involve in the dynamic bone remodelling in coordination with osteoblasts. Disruption of this regulatory balance between these cells or any imbalance in bone remodelling caused by a higher rate of resorption over construction of bone results in a decrease of bone matrix including bone mineral density (BMD). These osteoclast-dominant effects result in a higher risk of bone crack and joint demolition in several bone-related diseases, including osteoporosis and rheumatoid arthritis (RA). Tridax procumbens is a very interesting perennial plant and its secondary metabolites called here T. procumbens flavonoids (TPFs) are well-known phytochemical agents owing to various therapeutic practices such as anti-inflammatory, anti-anaemic and anti-diabetic actions. This review designed to focus the systematic convention concerning the medicinal property and mechanism of actions of TPFs for the management of bone-related diseases. Based on the current literature, the review offers evidence-based information of TPFs for basic researchers and clinicians for the prevention and treatment of bone related diseases, including osteoporosis. It also emphasizes the medical significance for more research to comprehend the cellular signalling pathways of TPFs for the regulation of bone remodelling and discusses the possible promising ethnobotanical resource that can convey the preclinical and clinical clues to develop the next generation therapeutic agents for the treatment of bonerelated disorders.

Effect of calcium and vitamin D supplementation with and without collagen peptides on bone turnover in postmenopausal women with osteopenia.

OBJECTIVES: Collagen peptides (CPs) seem to exert beneficial effects on bone and may have a role as a treatment option. In the present randomized prospective study, we aimed to examine the efficacy, as expressed by changes in P1NP and CTX, and the tolerability of 3-month supplementation of calcium, vitamin D with or without bioactive CPs in postmenopausal women with osteopenia. METHODS: Fifty-one female, postmenopausal women with osteopenia were allocated to two groups: Group A received a sachet containing 5 g CPs, 3.6 g calcium lactate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 and group B received a chewable tablet containing 1.25 g calcium carbonate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 daily. RESULTS: In group A, the P1NP levels significantly decreased by 13.1% (p<0.001) and CTX levels decreased by 11.4% (p=0.058) within 3 months of supplementation. In group B, P1NP and CTX did not change. Group A presented better compliance in comparison to group B and no adverse events contrary to group B. CONCLUSIONS: These findings may reflect the reduction of the increased bone turnover in postmenopausal women with the use of calcium, vitamin D and CPs supplements. The addition of CPs in a calcium and vitamin D supplement may enhance its already known positive effect on bone metabolism. Clinical Trial ID: NCT03999775.

Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix.

Studies of biological systems typically require the application of several complementary methods able to yield statistically-relevant results at a unique level of sensitivity. Combined X-ray fluorescence and ptychography offer excellent elemental and structural imaging contrasts at the nanoscale. They enable a robust correlation of elemental distributions with respect to the cellular morphology. Here we extend the applicability of the two modalities to higher X-ray excitation energies, permitting iron mapping. Using a long-range scanning setup, we applied the method to two vital biomedical cases. We quantified the iron distributions in a population of macrophages treated with Mycobacterium-tuberculosis-targeting iron-oxide nanocontainers. Our work allowed to visualize the internalization of the nanocontainer agglomerates in the cytosol. From the iron areal mass maps, we obtained a distribution of antibiotic load per agglomerate and an average areal concentration of nanocontainers in the agglomerates. In the second application we mapped the calcium content in a human bone matrix in close proximity to osteocyte lacunae (perilacunar matrix). A concurrently acquired ptychographic image was used to remove the mass-thickness effect from the raw calcium map. The resulting ptychography-enhanced calcium distribution allowed then to observe a locally lower degree of mineralization of the perilacunar matrix.

Bone Health Index and bone turnover in pediatric patients with type 1 diabetes mellitus and poor metabolic control.

BACKGROUND: There is a need for a non-invasive, affordable, and reliable method for bone health screening in pediatric patients at risk. OBJECTIVE: To assess Bone Health Index (BHI) in pediatric patients with type 1 diabetes (T1D) and its relation to bone metabolism, age at onset, duration, control, and insulin dose. SUBJECTS AND METHODS: Left-hand radiographs were obtained from 65 patients with T1D, mean age 11.23 ± 3.89 years, mean disease duration 5.23 ± 3.76 years and mean glycosylated hemoglobin (HbA1c)-83 mmol/mol (9.7%). Blood and 24 hours urine samples were collected for bone and mineral metabolism assessment. BoneXpert was used to determine BHI, Bone Health Index standard deviation score (BHI SDS), and bone age. RESULTS: Mean BHI SDS was -1.15 ± 1.19 (n = 54). In 20.37% (n = 11) BHI SDS was < -2SD with mean value -2.82 ± 0. 69, P < .001. These patients had lower levels of beta cross laps (0.77 ± 0.33 ng/mL vs 1.17 ± 0.47 ng/mL), osteocalcin (47.20 ± 14.07 ng/mL vs 75.91 ± 32.08 ng/mL), serum magnesium (0.79 ± 0.05 mmol/L vs 0.83 ± 0.06 mmol/L) and phosphorus (1.48 ± 0.29 mmol/L vs 1.71 ± 0.28 mmol/L) but higher ionized calcium (1.29 ± 0.04 mmol/L vs 1.26 ± 0.05 mmol/L), P < .05, compared to patients with BHI SDS in the normal range. We found a positive correlation between BHI SDS and age at manifestation (r = 0.307, P = 0.024) and a negative one with disease duration (r = -0.284, P = .038). No correlations were found with HbA1c, insulin dose, height, weight, BMI. CONCLUSIONS: To the best of our knowledge, this is the first study to assess bone health in pediatric patients with T1D using BHI. We found significantly decreased cortical bone density and bone turnover in 20.37%. Earlier age at onset and diabetes duration may have a negative impact on cortical bone density in patients with poor control. Longitudinal studies are needed to follow changes or to assess future interventions.

Skeletal impact of 17ß-estradiol in T cell-deficient mice: age-dependent bone effects and osteosarcoma formation.

Estrogen (E2)-dependent ER+ breast cancer, the most common breast cancer subtype, is also the most likely to metastasize to bone and form osteolytic lesions. However, ER+ breast cancer bone metastasis human xenograft models in nude mice are rarely studied due to complexities associated with distinguishing possible tumoral vs. bone microenvironmental effects of E2. To address this knowledge gap, we systematically examined bone effects of E2 in developing young (4-week-old) vs. skeletally mature (15-week-old) female Foxn1nu nude mice supplemented with commercial 60-day slow-release E2 pellets and doses commonly used for ER+ xenograft models. E2 pellets (0.05-0.72 mg) were implanted subcutaneously and longitudinal changes in hind limb bones (vs. age-matched controls) were determined over 6 weeks by dual-energy X-ray absorptiometry (DXA), microCT, radiographic imaging, and histology, concurrent with assessment of serum levels of E2 and bone turnover markers. All E2 doses tested induced significant and identical increases in bone density (BMD) and volume (BV/TV) in 4-week-old mice with high bone turnover, increasing bone mineral content (BMC) while suppressing increases in bone area (BA). E2 supplementation, which caused dose-dependent changes in circulating E2 that were not sustained, also led to more modest increases in BMD and BV/TV in skeletally mature 15-week-old mice. Notably, E2-supplementation induced osteolytic osteosarcomas in a subset of mice independent of age. These results demonstrate that bone effects of E2 supplementation should be accounted for when assessing ER+ human xenograft bone metastases models.

The bone hormones and their potential effects on glucose and energy metabolism.

The bones form the framework of our body. We know that bones protect our vital organs, regulate calcium and phosphorous homeostasis, and function as a site of erythropoiesis. More recently, however, the identification of bone hormones has allowed us to envision bones as endocrine organs too. Within the last few years, the bone hormones osteocalcin and lipocalin 2 have been implicated with glucose and energy metabolism. We systematically reviewed articles surrounding this subject and found a clear relationship between the osteocalcin levels and glucose tolerance and insulin sensitivity. We also found that many journals have shown the detrimental effects of an absences of lipocalin 2 from adipocytes. As osteocalcin administration to mice showed decreased blood glucose levels and promoted glucose tolerance and insulin sensitivity. Future studies could perhaps explore the use of osteocalcin as a supplement for type 2 diabetes.

Effect of calcium intake and the dietary cation-anion difference during early lactation on the bone mobilization dynamics throughout lactation in dairy cows.

This study investigated the consequences of a low supply of dietary Ca with or without a low dietary cation-anion difference (DCAD) during early lactation on bone mobilization and reconstitution during lactation and on the dynamics of milk Ca content. Fifteen multiparous Holstein cows were distributed among 3 treatments 5 weeks before their expected calving date. These treatments differed based on the provision of diets through the first 10 weeks of lactation. During this period, the control treatment (NCa) consisted of a diet providing 100% of the Ca requirement, with a DCAD of 200 mEq/kg dry matter (DM). The LCa (low Ca) and LCaLD (low Ca, low DCAD) treatments consisted of diets providing 70% of the Ca requirement, with a DCAD of 200 and 0 mEq/kg DM, respectively. After 10 weeks, all cows received the same total mixed ration, which was formulated to meet 100% of the Ca requirement. LCa and LCaLD tended to decrease the body retention of Ca at 3 weeks of lactation compared with NCa but affected neither the dynamics of the blood biomarkers of bone formation and resorption during lactation nor the body retention of Ca at 17 weeks of lactation. Cows almost entirely compensated for the decrease in Ca supply caused by LCa and LCaLD by increasing their apparent digestive absorption of Ca at 3 weeks of lactation, whereas their apparent digestive absorption was unaffected by the treatments at 17 weeks of lactation. Milk production tended to be lower throughout lactation with LCa and LCaLD compared with NCa, with a mean difference of 2 kg/d. The results of this study also indicated that measuring the dynamics of milk Ca content during lactation cannot be considered effective for indirectly estimating the dynamics of bone mobilization in cows. The results also suggested that limited Ca intake at the beginning of lactation may have deleterious effects on milk production.

Updating the role of matrix metalloproteinases in mineralized tissue and related diseases.

Bone development and healing processes involve a complex cascade of biological events requiring well-orchestrated synergism with bone cells, growth factors, and other trophic signaling molecules and cellular structures. Beyond health processes, MMPs play several key roles in the installation of heart and blood vessel related diseases and cancer, ranging from accelerating metastatic cells to ectopic vascular mineralization by smooth muscle cells in complementary manner. The tissue inhibitors of MMPs (TIMPs) have an important role in controlling proteolysis. Paired with the post-transcriptional efficiency of specific miRNAs, they modulate MMP performance. If druggable, these molecules are suggested to be a platform for development of "smart" medications and further clinical trials. Thus, considering the pleiotropic effect of MMPs on mammals, the purpose of this review is to update the role of those multifaceted proteases in mineralized tissues in health, such as bone, and pathophysiological disorders, such as ectopic vascular calcification and cancer.

The Effect of Dried Beancurd on Bone Mineral Density in Postmenopausal Chinese Women: A 2-Year Randomized Controlled Trial.

Soy foods contain several components such as isoflavones, calcium and protein that potentially modulate bone turnover and increase bone mineral density (BMD) in postmenopausal women. The study is to evaluate the effect of dried beancurd supplementation on skeletal health in postmenopausal Chinese women. Three hundred postmenopausal women aged 50-65 years were assigned into two groups, receiving 100 g dried beancurd or rice cake a day for 2 years. BMD at the lumbar spine and right proximal femur were measured with a dual-energy X-ray absorptiometry. The bone turnover biomarkers of serum alkaline phosphatase (ALP), bone Gla protein (BGP) and urinary N-telopeptide cross-links of collagen normalized for creatinine (NTX/CRT) were also determined. Serum isoflavone concentration was analyzed by high performance liquid chromatography. The 2-year dried beancurd supplementation generated a significant increase in lumbar spine BMD. An obvious decrease was found in urinary NTX/CRT, and a significant increase was detected in serum isoflavone concentration. The dried beancurd supplementation had no effect on changes of right proximal femur BMD and concentrations of serum ALP and BGP. Daily supplementation of dried beancurd could increase BMD of lumbar spine, but does not slow bone loss at right proximal femur in postmenopausal Chinese women.

Effects of l-carnitine supplementation on cardiovascular and bone turnover markers in patients with pemphigus vulgaris under corticosteroids treatment: A randomized, double-blind, controlled trial.

Pemphigus vulgaris (PV) is a severe, bullous, autoimmune disease of the skin and mucous membranes. Corticosteroids are usually the main core treatment for controlling PV, which could lead to several side effects such as insulin resistance, osteoporosis, and cardiovascular disorders. The aim of this study is to evaluate the protective effects of l-carnitine (LC) supplementation in PV patients under corticosteroid treatment. In this randomized, double-blind, placebo-controlled clinical trial, 48 patients with PV were divided randomly into two groups to receive 2 g LC (n = 24) or a placebo (n = 24) for 8 weeks, respectively. Serum levels of osteopontin (OPN), bone morphogenic protein 4 (BMP4), cystatin C, systolic and diastolic blood pressure, 25 hydroxyvitamin D3, and LC were evaluated at the beginning and at the end of the study. LC supplementation demonstrated a significant increase in serum carnitine (p < .001). In addition, at the end of the trial, LC supplementation significantly decreased serum BMP4 (p = .003), OPN (p = .03), and cystatin C (p = .001) levels. There was no significant effect on blood pressure in comparison with the placebo. During study, no harmful side effects were reported by patients. These findings indicate that LC supplementation significantly leads to favorable changes in OPN, BMP4, and cystatin C in PV patients under corticosteroid therapy. However, further investigations are required to confirm these results.

On the genetic determinants of hypovitaminosis D.

Hypovitaminosis D, defined by low serum levels of 25(OH)D, is a recognized worldwide public health problem. The most accepted definition considers that deficiency occurs with serum levels fall below 12 ng/ml of 25(OH)D. Long term vitamin D deficiency results in decreased bone mineralization, secondary hyperparathyroidism, increased cortical bone loss (pathogenesis of osteoporosis and hip fractures), differentiation and division of various cell types, muscle strength, diabetes type 2, blood pressure, etc. Twin- and family-based studies indicate that genetic factors influence serum 25(OH)D levels. Genetic studies have shown single-nucleotide polymorphisms (SNPs) are linked to low serum 25(OH)D concentrations through changes in the activity of the enzymes of the 1a,25(OH)2D metabolic pathway. Carriers of high genetic risk scores would need a h igher amount of vitamin D supplementation to achieve adequate serum 25(OH)D concentrations. Clinicians would not need to indicate studies to identify patients with vitamin D insufficiency of genetic origin. They should instruct their patients on their own care, to control the intake of vitamin D and the serum 25(OH)D levels until the latter are adequate. Overall, the literature reveals that the consequences of hypovitaminosis D on bone health are observed in old and infrequently in young subjects. A probable explanation for the latter is: if the rate of bone remodeling allows it, bone tissue has endogenous (genetics, hormones) and exogenous determinants (diet, physical activity) that may compensate the variables of bone health. The consequences of vitamin D deficit on bone health, has not been completely uncovered.

La hipovitaminosis D, definida por bajos niveles séricos de 25(OH)D (<12 ng/ml), es un reconocido problema de salud pública mundial. La deficiencia de vitamina D a largo plazo resulta en una disminución de la mi neralización ósea, hiperparatiroidismo secundario, pérdida de hueso cortical (patogénesis de la osteoporosis y fracturas de cadera), diferenciación y división de varios tipos de células, fuerza muscular, diabetes tipo 2, pres ión arterial, etc. Estudios genéticos han demostrado que algunos "polimorfismos de un solo nucleótido" (SNP) están relacionados con bajas concentraciones séricas de 25(OH)D a través de reducción en la actividad de las enzimas implicadas en la síntesis de 1a,25(OH)2D. Los médicos no necesitan indicar un estudio genético para identificar a la insuficiencia de vitamina D de causa genética. Bastará con instruir a los pacientes sobre su propio cuidado y controlar la ingesta de vitamina D y los niveles séricos de 25(OH)D hasta que estos últimos sean adecuados. En general, la literatura revela que las consecuencias de la hipovitaminosis D sobre la salud ósea se observan en las personas añosas y con poca frecuencia en sujetos jóvenes. Una explicación probable para esta situación es: si la tasa de remodelación ósea lo permite, el tejido óseo tiene factores endógenos (genéticos, hormonales) y exógenos (dieta, actividad física) que pueden compensar las variables de la salud ósea. Las consecuencias del déficit de vitamina D sobre la salud ósea aún no se conocen completamente.

On the genetic determinants of hypovitaminosis D

Hypovitaminosis D, defined by low serum levels of 25(OH)D, is a recognized worldwide public health problem. The most accepted definition considers that deficiency occurs with serum levels fall below 12 ng/ml of 25(OH)D. Long term vitamin D deficiency results in decreased bone mineralization, secondary hyperparathyroidism, increased cortical bone loss (pathogenesis of osteoporosis and hip fractures), differentiation and division of various cell types, muscle strength, diabetes type 2, blood pressure, etc. Twin- and family-based studies indicate that genetic factors influence serum 25(OH)D levels. Genetic studies have shown single-nucleotide polymorphisms (SNPs) are linked to low serum 25(OH)D concentrations through changes in the activity of the enzymes of the 1α,25(OH)2D metabolic pathway. Carriers of high genetic risk scores would need a h igher amount of vitamin D supplementation to achieve adequate serum 25(OH)D concentrations. Clinicians would not need to indicate studies to identify patients with vitamin D insufficiency of genetic origin. They should instruct their patients on their own care, to control the intake of vitamin D and the serum 25(OH)D levels until the latter are adequate. Overall, the literature reveals that the consequences of hypovitaminosis D on bone health are observed in old and infrequently in young subjects. A probable explanation for the latter is: if the rate of bone remodeling allows it, bone tissue has endogenous (genetics, hormones) and exogenous determinants (diet, physical activity) that may compensate the variables of bone health. The consequences of vitamin D deficit on bone health, has not been completely uncovered.

La hipovitaminosis D, definida por bajos niveles séricos de 25(OH)D (<12 ng/ml), es un reconocido problema de salud pública mundial. La deficiencia de vitamina D a largo plazo resulta en una disminución de la mi neralización ósea, hiperparatiroidismo secundario, pérdida de hueso cortical (patogénesis de la osteoporosis y fracturas de cadera), diferenciación y división de varios tipos de células, fuerza muscular, diabetes tipo 2, pres ión arterial, etc. Estudios genéticos han demostrado que algunos "polimorfismos de un solo nucleótido" (SNP) están relacionados con bajas concentraciones séricas de 25(OH)D a través de reducción en la actividad de las enzimas implicadas en la síntesis de 1α,25(OH)2D. Los médicos no necesitan indicar un estudio genético para identificar a la insuficiencia de vitamina D de causa genética. Bastará con instruir a los pacientes sobre su propio cuidado y controlar la ingesta de vitamina D y los niveles séricos de 25(OH)D hasta que estos últimos sean adecuados. En general, la literatura revela que las consecuencias de la hipovitaminosis D sobre la salud ósea se observan en las personas añosas y con poca frecuencia en sujetos jóvenes. Una explicación probable para esta situación es: si la tasa de remodelación ósea lo permite, el tejido óseo tiene factores endógenos (genéticos, hormonales) y exógenos (dieta, actividad física) que pueden compensar las variables de la salud ósea. Las consecuencias del déficit de vitamina D sobre la salud ósea aún no se conocen completamente.