Reference intervals for CTX and P1NP in a multi-ethnic Malaysian cohort.

BACKGROUND: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population. METHODS: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches. RESULTS: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L. CONCLUSION: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population.

Application of bone metabolic parameters in the diagnosis of growing pains.

OBJECTIVE: The present study aimed to assess the diagnostic significance of serum bone metabolic parameters in children with growing pains (GPs). METHODS: All patients diagnosed with GP and healthy controls matched with age and gender were recruited at the outpatient clinic of Children's Hospital at Zhejiang University School of Medicine from August 2016 to August 2021. In all subjects, serum levels of calcium (Ca), phosphorus (P), procollagen type-I N-terminal (PINP), parathormone (PTH), 25-hydroxyvitamin D (25-(OH)D), osteocalcin (OC), N-terminal cross-linked telopeptides of type-I collagen (CTX), and tartrate-resistant acid phosphatase type 5b (TRACP5b) were investigated. The univariate analysis, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve were used to identify the bone metabolic parameters factors for diagnosing GP. RESULTS: We enrolled 386 children with GP and 399 healthy controls in present study. The mean age of GP group was 5.319 years, and, primarily, the subjects were preschool-age children. The gender ratio (male-to-female) was 1.27 in GP group. After adjusting for age and gender, we identified that the serum levels of Ca (p < 0.001, OR: 25.039), P (p = 0.018, OR: 2.681), PINP (p < 0.001, OR: 1.002), and PTH (p = 0.036, OR: 0.988) were independent diagnostic factors associated with GP. Area under curve (AUC) of the ROC curves was in the order: PINP (0.612) > Ca (0.599) > P (0.583) > PTH (0.541). A combination of independent diagnostic factors and multivariable logistic regression analysis provided a refined logistic regression model to improve the diagnostic potential, of which the AUC had reached 0.655. CONCLUSIONS: Serum levels of Ca, P, PINP, and PTH could be independent diagnostic factors associated with GP. The logistic model was significantly superior to bone metabolic parameters for diagnosing GP.

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.

Fructus Ligustri Lucidi aqueous extract promotes calcium balance and short-chain fatty acids production in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. AIM OF THE STUDY: To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. MATERIALS AND METHODS: OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. RESULTS: The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. CONCLUSIONS: FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial.

Effectiveness of electroacupuncture as a treatment for osteoporosis: A systematic review and meta-analysis.

BACKGROUND: Osteoporosis (OP) results in an increased risk of fragility fractures, representing a major public health problem. In preventing OP, complementary and alternative medicine, such as acupuncture, was recommended because of the low efficiency and side effects of medications. Recently, there is insufficient evidence on electroacupuncture as an effective therapy for OP management. Hence, we evaluated the effectiveness of electroacupuncture for OP treatment. METHODS: We conducted a systematic review and meta-analysis of clinical studies on patients with OP. Five databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang) were searched from the earliest publication date to March 12, 2020. Randomized controlled trials (RCTs) were included if electroacupuncture was applied as the sole treatment or as an adjunct to other treatments compared with medications in patients with OP. The measurement outcomes included serum aminoterminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX) levels, bone mineral density (BMD) of lumbar, and visual analog scale scores for OP-related pain. Acupoints were extracted when available. RESULTS: In total, 11 RCTs involving 731 participants were included for further meta-analysis. The meta-analysis showed that the use of electroacupuncture as a sole treatment or as an adjunct to other treatments could relieve OP-related pain compared with medications [mean difference (MD) =  -0.58, 95% confidence interval (CI); MD =  -0.97 to -0.19, P = .003, I2 = 88%; MD =  -1.47, 95% CI = -2.14 to -0.79, P < .001, I2 = 96%). Meanwhile, the results showed a favorable effect of electroacupuncture on decreasing serum beta-CTX levels. However, there were no significant differences in serum PINP levels and BMD of lumbar. Shenshu (BL23) was the most frequent acupoint stimulation among these studies. CONCLUSIONS: The application of electroacupuncture as an independent therapy or as an adjunct to other treatments might attenuate OP-related pain and serum beta-CTX levels. However, to overcome the methodological shortcomings of the existing evidence, due to a small size of samples and high risk of bias in these included RCTs, further rigorous studies are required.

Elevated Urate Levels Do Not Alter Bone Turnover Markers: Randomized Controlled Trial of Inosine Supplementation in Postmenopausal Women.

OBJECTIVE: Observational studies have consistently demonstrated that serum urate level positively correlates with bone mineral density (BMD). We undertook this study to determine whether moderate hyperuricemia induced by inosine supplements influences bone turnover markers in postmenopausal women over a 6-month period. METHODS: One hundred twenty postmenopausal women were recruited for a 6-month randomized, double-blind, placebo-controlled trial. Key exclusion criteria were osteoporosis, previous fragility fracture, bisphosphonate therapy, gout, kidney stones, and a urine pH level of ≤5.0. Participants were randomized in a 1:1 ratio to receive placebo or inosine. The coprimary end points were change in levels of N-propeptide of type I procollagen (PINP) and change in levels of ß-C-telopeptide of type I collagen (ß-CTX). Change in BMD, as measured by dual x-ray absorptiometry, was an exploratory end point. RESULTS: Administration of inosine led to a significant increase in serum urate concentration over the study period (P < 0.0001 for all follow-up time points). At week 26, the mean change in serum urate concentration was +0.13 mmoles/liter (+2.2 mg/dl) in the inosine group and 0.00 mmoles/liter (0 mg/dl) in the placebo group. There was no difference in PINP or ß-CTX levels between groups over the 6 months. There were no significant changes in bone density between groups over the 6 months. Adverse events and serious adverse events were similar between the 2 groups. CONCLUSION: This clinical trial shows that although inosine supplementation leads to sustained increases in serum urate levels over a 6-month period, it does not alter markers of bone turnover in postmenopausal women. These findings do not support the concept that urate has direct biologic effects on bone turnover.

A Dairy Product to Reconstitute Enriched with Bioactive Nutrients Stops Bone Loss in High-Risk Menopausal Women without Pharmacological Treatment.

Osteoporosis is a multifactorial disease characterized by the loss of bone mass and deterioration of the internal structure of the bone, increasing the risk of fractures, and is becoming an economic and social problem. The main treatment is pharmacological, however, the population demands other therapies, such as foods with nutrients beneficial to bone health. Seventy-eight healthy menopausal women at risk of osteoporosis or untreated osteopenia were recruited for a randomized, parallel, double-blind clinical trial with two intervention groups: one group consumed a serving a day of the experimental enriched product (experimental group (EG)) and the other group (control group (CG)) consumed the same product without enrichment. The main objective was to compare the effect of consuming a dairy preparation to reconstitute, similar to yogurt when prepared, enriched in calcium, vitamin D, vitamin K, vitamin C, zinc, magnesium, L-leucine and probiotic (Lactobacillus plantarum 3547) on bone metabolism markers for 24 weeks. The EG showed a significantly increased bone mass compared to the CG (0.01 ± 0.03 vs. -0.01 ± 0.03 kg; p < 0.05). In addition, the EG maintained their bone mineral density (BMD) compared to the CG, whose BMD significantly decreased at the end of the study. For biochemical markers, the EG significantly increased the serum levels of the N-terminal propeptide of type I collagen (P1NP) bone formation marker (13.19 ± 25.17 vs. -4.21 ± 15.62 ng/mL; p < 0.05), and decreased the carbo-terminal telopeptide of type I collagen (CTx) bone resorption marker compared to the CG (-0.05 ± 0.19 vs. 0.04 ± 0.14 ng/mL; p < 0.05). On the other hand, the EG exhibited a significantly decreased systolic and diastolic blood pressure compared to the start of the study. Finally, the EG significantly increased their dietary calcium and vitamin D intake compared to the CG. In conclusion, the regular consumption of a dairy product to reconstitute enriched with bioactive nutrients improves bone health markers in menopausal women at risk of osteoporosis without pharmacological treatment.

Effects of whole-body vibration training on bone density and turnover markers in adolescent swimmers.

Background Whole-body vibration training has recently been proposed as a complementary training modality to improve the bone health of adolescent swimmers. However, there is no longitudinal study regarding the effects of this training combination on bone metabolism. Therefore, the main goal was to analyze the effects of swimming and vibration training on bone turnover markers during adolescence. Methods The present study included 68 adolescent swimmers and 41 normoactive controls (CON). Swimmers were randomly selected to either continue with their regular swimming training (SWI) or participate in an additional vibration protocol (VIB). Anthropometric measurements and serum level determinations of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide crosslaps (CTX) were performed before and after the 6-month intervention. Results Statistically significant group by time interactions were found for both bone formation markers. VIB showed a decrease over time in OC (baseline: 101.4 µg/mL, follow-up: 82.8 µg/mL, p < 0.05) and P1NP (baseline: 528.4 µg/mL, follow-up: 389.0 µg/mL, p < 0.05) and SWI had analogous reductions in P1NP (baseline: 685.8 µg/mL, follow-up: 542.0 µg/mL, p < 0.05), whereas CON experienced an increase in OC levels (baseline: 94.4 µg/mL, follow-up: 103.4 µg/mL, p < 0.05). After stratifying the sample according to the pubertal status, similar interactions were observed. Conclusions The combination of swimming training and this particular vibration protocol led to a decrease in bone formation markers, especially during early puberty. Whole-body vibration might not induce an osteogenic stimulus in adolescent swimmers.

Skeletal and mineral metabolic effects of risedronate in a rat model of high-turnover renal osteodystrophy.

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.

Imaging, biomarker and invasive assessment of diffuse left ventricular myocardial fibrosis in atrial fibrillation.

BACKGROUND: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. METHODS: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. RESULTS: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. CONCLUSION: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.

Effect of vitamin D fortified foods on bone markers and muscle strength in women of Pakistani and Danish origin living in Denmark: a randomised controlled trial.

BACKGROUND: Deficient and insufficient vitamin D status (defined as serum 25(OH)D < 30 nmol/L and > 50 nmol/L) is prevalent worldwide and associated with decreased muscle strength and poor bone health. We aimed to investigate the effect of vitamin D fortification on bone markers and muscle strength among younger adult women at risk of vitamin D deficiency. METHODS: A 12-week randomised double-blinded placebo-controlled winter intervention trial, providing 30 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp-bread or similar placebo products. Participants were 143 women of Danish and Pakistani origin 18-50 years of age, living in Denmark, randomised into four groups stratified by ethnicity. Serum 25-hydroxyvitamin D (25(OH)D) by LC-MS/MS and the secondary endpoints: four specific bone markers (osteocalcin (OC), Bone specific Alkaline Phosphatase (BALP), Procollagen type 1 amino-terminal propeptide (P1NP), C-terminal crosslinked telopeptide of type 1 collagen (CTX)) and three muscle strength measures (handgrip, knee extension strength, chair-standing), were assessed using one-way ANOVA, Tukey HSD and subsequent linear ANCOVA models, adjusted for relevant covariates. RESULTS: Significantly increased serum 25(OH)D concentration from 53.3 (17) to 77.8 (14) nmol/L and from 44.5 (21) to 54.7 (18) nmol/L among Danish and Pakistani women in the fortified groups, respectively (P <  0.05). The bone turnover markers OC, BALP, P1NP and CTX did not change significantly. Muscle strength by handgrip, knee extension and chair-standing test did not change significantly following the intervention. CONCLUSIONS: Consumption of vitamin D fortified foods for 12 weeks did not result in significant changes of the bone turnover markers OC, BALP, P1NP and CTX. Muscle strength measured as hand grip strength, knee extension strength and chair-standing did not change significantly following the intervention.

Effects of resveratrol supplementation on bone biomarkers: a systematic review and meta-analysis.

The current study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on resveratrol and bone health biomarkers. PubMed, Scopus, and Web of Science (until September 2018) were searched to identify the potential RCTs with information on resveratrol supplementation and bone metabolism biomarkers. Mean differences (MD) were analyzed using a random-effects model. Pooling six RCTs (eight treatment arms with 264 subjects) together identified no significant reduction of serum Ca, osteocalcin, C-terminal telopeptide of type I collagen, and procollagen I N-terminal propeptide values after resveratrol supplementation over placebo treatment. However, a significant increase in serum alkaline phosphatase (ALP) (MD: 5.69 mg/mL, 95% CI: 3.58-7.80, I2  = 95.7%, P < 0.001) and bone alkaline phosphatase (BAP) (MD: 10.57 mmHg, 95% CI: 5.36-15.78, I2  = 99.2%, P < 0.001) values was observed after resveratrol treatment relative to placebo. The findings of this study indicate that resveratrol supplementation increased some key bone biomarkers, such as ALP and BAP. Further precise clinical trials of the effects of resveratrol supplementation on bone health should be conducted.

Temporal Change in Biomarkers of Bone Turnover Following Late Evening Ingestion of a Calcium-Fortified, Milk-Based Protein Matrix in Postmenopausal Women with Osteopenia.

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.

Effect of Vitamin D Supplementation on Bone Turnover Markers During HIV Pre-Exposure Prophylaxis Using Tenofovir Disoproxil Fumarate-Emtricitabine in Men Who Have Sex with Men.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) reduces bone mineral density in HIV-uninfected men who have sex with men (MSM). We hypothesized that PrEP with TDF-FTC would increase bone turnover markers (BTMs) at week 24 and that vitamin D supplementation from weeks 24 to 48 would blunt this increase. Participants were from a cohort of 398 MSM and transgender women who received daily TDF-FTC for PrEP. At week 24, a prospective intervention group initiated vitamin D3 4,000 IU daily. Concurrent controls were selected from the cohort who took ≤400 IU/day of vitamin D3 matched by age, race, and body mass index. The primary endpoint was the change in procollagen-I N-terminal propeptide (P1NP) from weeks 24 to 48. Paired t-tests were used to compare changes in BTMs between intervention and controls. Among 48 intervention-control pairs, median age was 33 years. At baseline, 68.9% of the intervention group and 77.3% of controls were vitamin D sufficient (≥20 ng/mL, p = .94). P1NP, C-telopeptide, parathyroid hormone (PTH), and 25-OH vitamin D3 did not increase significantly at week 24. P1NP fell by a mean ± SD of -27.6 ± 49.9 pg/mL from weeks 24 to 48 with vitamin D and -2.5 ± 40.2 pg/mL in controls (p = .01). There were no significant between-group differences in the weeks 24-48 change in C-telopeptide, PTH, or 25-OH vitamin D3. Vitamin D3 supplementation with 4,000 IU/day resulted in a significant reduction in the BTM P1NP compared with controls, suggesting that this intervention has potential to improve bone health during PrEP.

Effects of Different Vitamin C-Enriched Collagen Derivatives on Collagen Synthesis.

Nutritional strategies to improve connective tissue collagen synthesis have garnered significant interest, although the scientific validity of these interventions lags behind their hype. This study was designed to determine the effects of three forms of collagen on N-terminal peptide of procollagen and serum amino acid levels. A total of 10 recreationally active males completed a randomized double-blinded crossover design study consuming either placebo or 15 g of vitamin C-enriched gelatin or hydrolyzed collagen (HC), or gummy containing equal parts of gelatin and HC. Supplements were consumed 1 hr before 6 min of jump rope. Blood samples were collected immediately prior to supplement consumption and 4 hr after jump rope. A subset of blood samples (n = 4) was collected for amino acid analysis 1 hr after ingestion. Consumption of an equivalent dose of each supplement increased amino acids in the circulation similarly across all interventions. N-terminal peptide of procollagen levels tended to increase ∼20% from baseline in the gelatin and HC interventions but not the placebo or gummy. These results suggest that vitamin C-enriched gelatin and HC supplementation may improve collagen synthesis when taken 1 hr prior to exercise. However, large variability was observed, which precluded significance for any treatment.

Efficacy and safety of recombinant human parathyroid hormone (1-34) are similar to those of alendronate in the treatment of postmenopausal osteoporosis.

The study evaluates efficacy and safety of recombinant human parathyroid hormone (1-34) [rhPTH (1-34)] and alendronate (ALN) in the treatment of postmenopausal osteoporosis.Totally 65 postmenopausal women with osteoporosis were divided into 2 groups. PTH group received daily subcutaneous injection of rhPTH (1-34), and ALN group were treated orally with ALN per week. Bone mineral density (BMD) of lumbar spine (1-4), femoral neck, and total hip, serum levels of calcium, phosphorus, total cholesterol, triglyceride, alkaline phosphatase (ALP), N-terminal propeptide of type I collagen (PINP), and C-telopeptide of type I collagen (CTX) were tested before treatment and at week 24 and 48 after treatment. Serum levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB) were measured before treatment and at week 48 after treatment.The rhPTH (1-34) increased BMD of lumbar spine (1-4), but decreased BMD of femoral neck and total hip at week 48 after treatment. By contrast, ALN enhanced BMD of lumbar spine (1-4) and femoral neck, but reduced BMD of total hip at week 48 after treatment. In PTH group, serum levels of PINP, ALP, and ß-CTX were significantly elevated above baseline at week 24 and 48 after treatment. Treatment with ALN decreased levels of PINP, ALP, and ß-CTX compared with baseline at week 24 and 48 after treatment. rhPTH (1-34) and ALN significantly decreased levels of PDGF-BB, but not levels of VEGF. rhPTH (1-34) increased levels of calcium, phosphorus and triglyceride, but decreased levels of total cholesterol. ALN increased levels of calcium and triglyceride, but reduced levels of phosphorus and total cholesterol. rhPTH (1-34) and ALN were safe in the treatment of postmenopausal osteoporosis.The study demonstrates that efficacy of rhPTH (1-34) on BMD of lumbar spine (1-4) is similar to that of alendronate in the treatment of postmenopausal osteoporosis. The effect of rhPTH (1-34) on BMD of femoral neck or total hip is weaker than that of ALN. In addition, rhPTH (1-34) increases BMD of lumbar spine (1-4) maybe by raising serum levels of VEGF, but reduces BMD of femoral neck and total hip maybe by decreasing serum levels of PDGF-BB.

The effects of ultraviolet supplementation to the artificial lighting on rats' bone metabolism, bone mineral density, and skin.

Working and living under artificial lighting environment for a long duration do not allow sufficient sunlight exposure, resulting in an adverse effect on bone. Common artificial light source, white LED light, does not include ultraviolet irradiation that plays an important role in bone metabolism. Ultraviolet supplementation in artificial lighting environment can be used to simulate the effect of sunlight irradiation on bone metabolism. In this paper, we report the effects of long-term exposure of low-dose ultraviolet irradiation on the rats' bones and skin. We studied the changes in body weight, bone metabolism markers, bone mass content, bone mineral density, and skin of rats, under long-term exposure of low-dose ultraviolet irradiation. We found that the rats exposed to ultraviolet irradiation showed an increase in bone formation rate, decrease in bone resorption rate, and improvement in bone mass content and bone mineral density without adverse effects on skins. This paper provides an effective basis for future application of LED light to create a healthier, safer, and more comfortable indoor lighting environment.

Effect of increasing doses of vitamin D on bone mineral density and serum N-terminal telopeptide in elderly women: a randomized controlled trial.

BACKGROUND: There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). OBJECTIVES: We conducted a randomized placebo-controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25-hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. METHODS: Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12-month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. RESULTS: The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N-telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12-month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. CONCLUSIONS: We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N-terminal telopeptides in elderly women with initially low serum 25OHD.

Effect of calcium citrate vs calcium carbonate on elevated parathyroid hormone after Roux-en-Y gastric bypass. A double-blinded, randomized trial.

OBJECTIVE: Following Roux-en-Y gastric bypass (RYGB), elevated parathyroid hormone (PTH) levels potentially harmful to bone health are commonly observed. Owing to assumed superior absorption, calcium citrate is often recommended over calcium carbonate following RYGB for the treatment of elevated PTH. We aimed to investigate the impact of either calcium carbonate or calcium citrate (1200 mg elementary calcium) in patients with elevated PTH levels following RYGB. DESIGN: Clinical, double-blinded, randomized controlled trial of a 12-week duration at a Danish University Hospital. PATIENTS AND MEASUREMENTS: Thirty-nine (no drop out) RYGB operated patients with elevated PTH levels (PTH > 6.9 pmol/L) and normal plasma levels of calcium and 25-hydroxyvitamin D were randomized to either calcium carbonate or calcium citrate (1200 mg elementary calcium/daily). We assessed change in PTH as the primary outcome. RESULTS: The effect of the two calcium formulations on change in PTH was comparable and neutral: -1.9% (calcium citrate) vs +0.9% (calcium carbonate), P = 0.680. Compared to the carbonate-treated group, the following bone turnover markers decreased significantly in the citrate-treated group: procollagen I N-terminal propeptide (-16.6% vs -3.2%, P = 0.021), osteocalcin (-17.2% vs -4.3%, P = 0.007) and bone-specific alkaline phosphatase (-5.9% vs 3.7%, P = 0.027) and remained significantly decreased after multivariable adjustment. CONCLUSION: Increasing the dose of calcium supplementation in RYGB operated patients with slightly elevated PTH levels does not normalize PTH levels, regardless of the type of supplement. Our results do not support recommending supplementation with calcium citrate over calcium carbonate in RYGB patients.

Cholecalciferol Supplementation Promotes Bone Turnover in Chinese Adults with Vitamin D Deficiency.

BACKGROUND: Bone turnover markers (BTMs) are proposed as alternative indicators for bone mineral density in diagnosis and management of osteoporosis. However, little is known about the effects of vitamin D supplementation on BTMs in nonwhite populations. OBJECTIVE: We aimed to investigate the responses in BTMs after vitamin D supplementation in Asians. METHODS: In this secondary data analysis of a randomized, double-blind, placebo-controlled trial, 448 Chinese adults [mean ± SD age: 31.9 ± 8.0 y; mean ± SD body mass index (kg/m2): 22.1 ± 2.6; 69% were women] with vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) received 2000 IU/d cholecalciferol or placebo for 20 wk. Serum concentrations of 25(OH)D, parathyroid hormone (PTH), calcium, and markers of bone formation and resorption were measured at weeks 0 and 20. Intention-to-treat analysis was applied, and between-group differences were compared by general linear models with adjustments. RESULTS: Cholecalciferol supplementation increased the serum bone alkaline phosphatase (BALP) concentration (+1.7 ± 1.9 µg/L) significantly more than placebo (+1.1 ± 1.7 µg/L; P = 0.004), but not circulating concentrations of procollagen type I N-terminal propeptide (PINP), ß-isomerized C-terminal telopeptide of type I collagen (ß-CTX), or tartrate-resistant acid phosphatase 5b (TRAP5b) (P ≥ 0.53). Notably, a pooled analysis indicated that changes in serum 25(OH)D were positively associated with changes in serum BALP, PINP, and TRAP5b (r = 0.07-0.16, P ≤ 0.02), but inversely with changes in PTH (r = -0.15, P < 0.001). Among cholecalciferol-treated participants, individuals who achieved serum 25(OH)D ≥75 nmol/L had greater increases in serum ß-CTX (224% compared with 146%; P = 0.02) and TRAP5b (22.2% compared with 9.1%; P = 0.007), but smaller decreases in serum calcium (-1.3% compared with -1.9%; P = 0.005) and calcium-phosphorus product (-2.6% compared with -3.3%; P = 0.02) compared with those with serum 25(OH)D <75 nmol/L. CONCLUSIONS: Daily supplementation with 2000 IU cholecalciferol for 20 wk may promote bone formation in Chinese adults with vitamin D deficiency. More studies are needed to elucidate the potential clinical implications of BTMs.This trial was registered at clinicaltrials.gov as NCT01998763.