Serum N-terminal Propeptide Of Type Research Articles

Correlation between bone density, bone metabolism markers with lipid metabolism markers and body mass index

PurposeWe aimed to explore the relationship between bone mineral density (BMD), bone metabolism markers, and blood lipid-related indicators, body mass index (BMI) in elderly individuals.MethodsA retrospective analysis was conducted on 710 patients. Patients’ gender, age, height, weight, bone density values, T-scores, bone metabolism markers (including serum N-terminal propeptide of type I collagen (s-PINP), serum C-terminal telopeptide of type I collagen (s-CTX) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and lipid-related indicators (including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and Castelli index 1 (TC/HDL-C index) and Castelli index 2 (LDL-C/HDL-C index) were recorded. Correlations between variables were analyzed, and patients were grouped according to gender and T-score for intergroup comparisons.ResultsHDL-C negatively correlates with BMD and s-CTX. TG, Castelli index, and BMI positively correlate with BMD. BMI negatively correlates with s-PINP. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. LDL-C positively correlates with BMD in males, and TC negatively correlates with s-PINP. In females, HDL-C negatively correlates with BMD, and s-CTX positively correlates with Castelli index. 1,25(OH)2D3 negatively correlates with TC, LDL-C, and Castelli index. TG and Castelli index were higher in normal bone mass group, while HDL-C is higher in the osteoporosis group. TG and BMI positively predicted bone mass density, while HDL-C negatively predicted bone mass density.ConclusionsHDL-C may have a predictive role in osteoporosis, particularly in women. The likelihood of osteoporosis is lower in individuals with high BMI or hyperlipidemia. Some lipid metabolism markers can be used to predict osteoporosis, and further research is needed.

Study on the Effect of Bushen Zhuanggu Tablet Combined with Conventional Regimen on Bone Mineral Density Improvement, Functional Recovery and Fracture Risk Prevention in Patients with Postmenopausal Osteoporosis.

This case-control study was to explore the effect of Bushen Zhuanggu tablet combined with routine regimen on bone mineral density (BMD) improvement, functional recovery, and fracture prevention in postmenopausal osteoporosis (PMOP) patients. 180 postmenopausal osteoporosis patients were randomly selected from communities A, B, and C cohorts as research subjects from January to May 2021. The study subjects were divided into three groups. The groups were in a 1 : 1 ratio according to the principles of nonrandomised, concurrent controlled trials, and methods. There were 60 participants in each group (group A, group B, and group C). Group A was treated with Bushen Zhuanggu tablet for antiosteoporosis + basic treatment (calcium supplement and vitamin D). Group C was given Bushen Zhuanggu tablet for antiosteoporosis intervention. Group B was given basic treatment (calcium supplement and vitamin D supplementation) as a control group. The follow-up time was 6 months after treatment. Finally, we compare the differences in calcium and phosphorus metabolism indexes, BMD, bone metabolism indexes, upper and lower limb muscle strength, and quality of life scores. Group A, B, and C's effective rate was 98.33%, 80.00%, and 93.33%, respectively. The group A's effective rate was significantly higher than that in group B and C, and the difference was statistically significant (P < 0.05). After 6 months intervention, the levels of serum Ca2+, serum phosphorus (P), serum creatinine (Cr), and parathyroid hormone (PTH) in 3 groups decreased. Ca, P, Scr, and PTH levels in group A were the lowest among study groups, and the difference was statistically significant (P < 0.05). The increase in the BMD of lumbar spine, the left femoral neck, and Ward's triangle area of the three groups were observed with the highest data in group A. After 6 months of treatment, the levels of serum N-terminal propeptide of type I procollagen, PINP, and serum osteocalcin (OC) increased, while the levels of β-cross-linked C-terminal telopeptide of type I collagen (β-CTX) and alkaline phosphatase (ALP) decreased in the three groups. The improvement of all bone metabolic indexes in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). The enhanced upper limb muscle strength and the shorter standing-walking timing test (TUGT) time were observed after 6 months of treatment. The improvement effect of upper and lower limb muscle strength in group A was significantly better than that in B and C groups, and the difference was statistically significant (P < 0.05). There were significant differences in physiological function, life function, general health status, physical pain, mental state, emotional function, vitality, and social function among the three groups after 6 months treatment, and the difference was statistically significant (P < 0.05). The score of quality of life in group A was higher than that in B and C groups, and the difference was statistically significant (P < 0.05). Bushen Zhuanggu tablet combined with conventional therapy is effective in the postmenopausal osteoporosis treatment, which effectively increase the BMD, regulate calcium and phosphorus metabolism, promote the recovery of limb function, prevent the recurrence of fracture, and improve the patients' quality of life. This treatment scheme is worth popularizing.

Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes.

BackgroundRecently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process.MethodsDmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12–20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16–20, N = 4–6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography.ResultsScl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas.ConclusionBLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin.

A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033.Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life.Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Time-Restricted Eating for 12 Weeks Does Not Adversely Alter Bone Turnover in Overweight Adults.

Weight loss is a major focus of research and public health efforts. Time-restricted eating (TRE) is shown to be effective for weight loss, but the impact on bone is unclear. Short-term TRE studies show no effect on bone mineral density (BMD), but no study has measured bone turnover markers. This secondary analysis examined the effect of 12 weeks of TRE vs. unrestricted eating on bone turnover and BMD. Overweight and obese adults aged 18–65 y (n = 20) were randomized to TRE (ad libitum 8-h eating window) or non-TRE. Serum N-terminal propeptide of type I collagen (P1NP), cross-linked N-telopeptide of type I collagen (NTX), and parathyroid hormone (PTH) levels were measured and dual-energy X-ray absorptiometry (DXA) scans were taken pre- and post-intervention. In both groups, P1NP decreased significantly (p = 0.04) but trended to a greater decrease in the non-TRE group (p = 0.07). The treatment time interaction for bone mineral content (BMC) was significant (p = 0.02), such that BMC increased in the TRE group and decreased in the non-TRE group. Change in P1NP was inversely correlated with change in weight (p = 0.04) overall, but not within each group. These findings suggest that TRE does not adversely affect bone over a moderate timeframe. Further research should examine the long-term effects of TRE on bone.

Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis.

The short-term effects of discontinuing long-term bisphosphonates are poorly characterized. This post hoc analysis investigated 1-12-month changes in bone mineral density (BMD) and bone turnover markers (BTM) after alendronate (ALN) discontinuation. Data were from a randomized, double-blind trial of MK-5442 (calcium-sensing receptor antagonist) following oral bisphosphonates, with placebo and continued ALN controls ( ClinicalTrials.gov NCT00996801). Postmenopausal women with osteoporosis had received oral bisphosphonate (≥ 3-4 preceding years; ALN for the 12 months pre-screening), continuing on ALN 70 mg/week (n = 87) or placebo (n = 88). At 12 months, least-squares mean percent changes from baseline BMD (placebo vs. ALN) were lumbar spine (LS): - 0.36 vs. 1.29, total hip: - 1.44 vs. 0.46, and femoral neck (FN): - 1.26 vs. - 0.08 (all P < 0.05). BTM levels increased by 1-3 months, to 12 months, with placebo vs. ALN (P < 0.001). FN BMD decline was greater in the placebo subgroup with higher urinary N-terminal cross-linked telopeptides of type I collagen/creatinine [uNTx/Cr] (P < 0.01), and higher serum N-terminal pro-peptide of type 1 collagen [P1NP] levels (P < 0.05), at baseline. There was a trend toward greater FN BMD loss with higher BTM levels at 3 and/or 6 months. Younger age and higher LS BMD at baseline were associated with greater LS BMD loss at 12 months (P = 0.04 and < 0.01, respectively); higher baseline FN BMD predicted greater FN BMD loss (P = 0.04). Early changes in BTM levels and BMD were observed after discontinuation of long-term ALN. Further characterization of factors associated with patients' risk of bone loss upon bisphosphonate discontinuation is warranted.

Increasing Consumption of Vegetables Decreases Acid Excretion and Bone Turnover Among Adults with Overweight and Obesity: An 8-Wk Randomized Controlled Trial

Abstract Objectives To investigate the extent to which increased vegetable consumption affects urinary acid excretion and serum bone markers. Epidemiological studies suggest vegetable intake is positively associated with bone health through several mechanisms such as reducing oxidative stress and inflammation or diet-induced metabolic acidosis. We hypothesized that increasing intake of vegetables to the amounts and types recommended by the Dietary Guidelines for Americans (DGA) is beneficial to bone health by suppressing bone turnover. Methods One-hundred and ten adults with overweight or obesity were recruited in a two-arm, parallel-designed, randomized controlled community-based 8-wk feeding intervention trial. The two arms included (1) attention control arm, and (2) active intervention arm during which participants received a variety of pre-packaged, minimally prepared fresh or frozen vegetables. Blood and urine samples were collected. One hundred-two participants completed the study. Results At baseline, there were no differences in urine pH (6.17 ± 0.42 vs 6.18 ± 0.41), urine titratable acid (21.0 ± 7.3 vs 20.7 ± 9.0 mEq/d), urine ammonia (324 ± 197 vs 348 ± 175 mg/d), serum N-terminal propeptide of type I procollagen (PINP, a bone formation marker, 27.8 ± 8.9 vs 26.3 ± 10.5 ng/ml), serum C-terminal telopeptide of type I collagen (CTX, a bone resorption marker, 0.36 ± 0.18 vs 0.34 ± 0.15 ng/ml), between the control and the intervention groups, respectively. There were no differences in the above parameters between the baseline and at the end of 8-wk for the control group. Compared to the baseline, increased intake of vegetables increased urine pH (6.33, P &amp;lt; 0.05) and serum PINP (29.7 ± 13.6 ng/ml, P &amp;lt; 0.05), and decreased urine titratable acid (17.0 ± 9.4 mEq/d, P &amp;lt; 0.05), urine ammonia (279 ± 151 mg/d, P &amp;lt; 0.05), and serum CTX (0.29 ± 0.11 ng/ml, P &amp;lt; 0.01). Conclusions These data demonstrate that increased vegetable consumption of the types and amounts recommended by the DGA decreases urinary acidity and has positive effects on bone turnover markers. Funding Sources This work was supported by the Agricultural Research Service of the United States Department of Agriculture, #3062–51,000-053–00D.

Effect of minimally invasive anterior lateral approach for total hip arthroplasty on serum type I collagen propeptide, tartrate-resistant acid phosphatase 5b and hip joint function in patients with femoral neck fracture

To analyze the level of serum N-terminal propeptide of type I precollagen (PINP) and tartrate resistant acid phosphatase 5b(TRACP-5b) in patients with femoral neck fracture(FNF) after minimally invasive anterior lateral approach with total hip arthroplasty and the effects of hip function. From September 2016 to May 2017, 98 cases of femoral neck fracture were divided into control group and observation group, 49 cases in each group. There were 49 patients in control group, including 30 males and 19 females, ranging in age from 63 to 72 years old, who underwent minimally invasive anterolateral total hip arthroplasty. There were 49 patients in observation group, including 29 males and 20 females, ranging in age from 62 to 73 years old, who underwent minimally invasive anterolateral total hip arthroplasty. The perioperative conditions(operation time, bleeding volume, incision length, hospitalization time), bone metabolism indexes including PINP, TRACP-5b, fibroblast growth factor(FGF), bone gla-protein(BGP), propetide carboxy-terminal procollagen (PICP), bone-specific alkaline phosphatase(BAP), and pain mediators such as prostaglandin E2 (PGE2) and 5-hydroxytrytamine (5-HT) levels were compared between the two groups. The hip joint function and complications were evaluated. The operation time of the observation group was longer than that of the control group(P<0.05); there was no significant difference in bleeding volume, incision length and hospitalization time between two groups(P>0.05). PINP, fibroblast growth factor, BGP, PICP and BAP in observation group were higher than those in control group 1 month after operation, and TRACP-5b was lower than those in control group(P<0.05); PGE2 and 5-HT in observation group 1 month after operation were lower than those before operation, and lower than those in control group(P<0.05). The excellent and good rate of hip function in observation group was higher than that in control group (P<0.05), and the incidence of complications was not significantly different from that in the control group (P>0.05). Minimally invasive anterolateral approach total hip arthroplasty is safe and reliable, and can improve hip function, improve bone metabolism, promote fracture healing, alleviate pain in patients with femoral neck fracture, which is worthy of promotion.

Changes in Dkk-1, sclerostin, and RANKL serum levels following discontinuation of long-term denosumab treatment in postmenopausal women.

The positive effects of denosumab (DMAb) on bone mineral density (BMD) are quickly reversible after its discontinuation. We investigated whether this rebound was associated with dysregulation of the Wnt canonical pathway and/or by the increase in the receptor-activator of nuclear factor-kappa B ligand (RANKL) serum levels. The study included patients (n = 15) with postmenopausal osteoporosis to whom DMAb was administered for 78 months and then discontinued. We collected BMD data at baseline/month 0 (M0), M60, M84 (6 months after last DMAb administration, coinciding when the next DMAb dose would typically be due), and after 3 and 12 months of follow-up (FU-M3 and FU-M12, respectively). Serum C-terminal telopeptide of type 1 collagen (CTX-I), Dickkopf-1 (Dkk-1), and sclerostin were measured at M0, M60, M84, FU-M3, and FU-M12. Serum N-terminal propeptide of type 1 procollagen (PINP) and RANKL were dosed at M60, M84, FU-M3, and FU-12. We found a significant decrease in the T-score at all sites at FU-M12, when compared to M84 (-0.51 ± 0.91 at the lumbar spine; -0.72 ± 0.33 at the total hip; and -0.42 ± 0.27 at the femoral neck, p < 0.05). After DMAb discontinuation (M84 vs FU M12) CTX-I, PINP increased already at FU-M3 (+0.921 ± 0.482 ng/mL, +126.60 ± 30.36 ng/mL, respectively, p < 0.01), RANKL increased at FU-M12 (+0.041 ± 0.062 ng/mL, p < 0.05), while Dkk-1 and sclerostin decreased at FU-M12 (-10.90 ± 11.80 and - 13.00 ± 10.52 pmol/L, respectively, p < 0.01). No changes in BMD or any of the markers were found between M60 and M84. RANKL serum levels progressively increased after discontinuation of long-term DMAb while Dkk-1 and sclerostin serum levels decreased. The increase in RANKL serum levels supports the hypothesis of a sudden loss of inhibition of the resting osteoclast line after DMAb clearance, with a hyperactivation of these cells. Our results suggest that the changes in serum Wnt inhibitors after DMAb suspension might represent a mere feedback response to the increased bone turnover.

Efficacy of long-term treatment with Teriparatide on osteoporotic intertrochanteric fracture in the elderly

Objective To observe the efficacy of long-term treatment with Teriparatide on osteoporotic intertrochanteric fracture in the elderly. Methods The elderly patients with osteoporotic intertrochanteric fracture meeting inclusion and exclusion criteria were recruited.They received proximal femoral nail anti-rotation(PFNA)surgery with the combined intakes of calcium of 600 mg/day and 1-alpha, 25-(OH)2-vitamin D3 analogs of 0.5 μg/day as a basic standard treatment protocol(BSTP). The study subjects included control group(n=10)who underwent PFNA surgery plus oral calcium and vitamin D supplements without teriparatide(20 μg/d), and the observation group who received PFNA surgery plus oral calcium and vitamin D supplements with teriparatide(20 μg/d), for more than twelve months or over at our department from October 2012 to February 2016.Gender, age, socio-demographics and clinical values of the American Society of Anesthesiologists(ASA)score, fracture types, preoperative serum albumin level, preoperative BMI, bone mineral density 1 week postoperatively, serum N-terminal propeptide of type I collagen(PINP)and C-terminal telopeptides of type 1 collagen(β-CTX)1 week postoperatively were matched between the two groups, no statistically significant difference was found(all P>0.05). Levels of PINP and β-CTX 3, 6 and 12 months postoperatively, BMD 1 year postoperatively, fracture healing time and complications were compared between the two groups.The prognosis of 1 case of patient undergoing conservative treatment was observed. Results There was no significant difference between the two groups in serum levels of PINP and β-CTX 1 week postoperatively(P=0.362 and 0.517, respectively). Serum level of PINP was significantly increased in observation group at 3, 6 and 12 months postoperatively versus at 1 week postoperatively(P=0.008, 0.001 and 0.004, respectively), while serum level of PINP had no significant difference in control group at 3, 6 and 12 months postoperatively versus at 1week postoperatively(P>0.05). Serum levels of PINP 3, 6 and 12 months postoperatively were higher in the observation group than in control(P=0.002, 0.002 and 0.000, respectively). In the observation group, serum β-CTX level reached the peak at 6 months after surgery, which was higher than that at 1 week after surgery(P=0.041), and slowly decreased at 12 months after surgery.In the control group, β-CTX slowly increased at 3, 6 and 12 months postoperatively versus at 1 week postoperatively(P>0.05). There was no significant difference in BMD of lumbar spine and contralateral hip between the two groups at 1 week postoperatively(P=0.440 and 0.325). At 1 year postoperatively versus at 1 week postoperatively, the BMD of lumbar spine and contralateral hip was increased(P=0.039 and 0.009)in the observation group, while was decreased(P>0.05)in control group.The fracture healing time was shorter in observation group than in control group(13.6±2.2 weeks vs.17.6±3.4 weeks, P=0.033). No one had a delayed fracture healing in observation group and 1 patient showed a delayed fracture healing in the control group.There were no complications such as lag screw sliding, refracture, pressure ulcer and deep vein thrombosis in both groups.The fracture nonunion was found in the patient undergoing conservative treatment after 20 months of teriparatide treatment. Conclusions The medium-and long-term of teriparatide treatment can significantly promote bone formation, improve BMD of the lumbar spine and hip, and shorten fracture healing time in patients with osteoporotic intertrochanteric fracture, but it is not a substitute for surgical treatment. Key words: Osteoporosis; Hip fractures; Teriparatide

Calcium and Bone Metabolism Indices.

Calcium and inorganic phosphate are of critical importance for many body functions, thus the regulations of their plasma concentrations are tightly controlled by the concerted actions of reabsorption/excretion in the kidney, absorption in the intestines, and exchange from bone, the major reservoir for calcium and phosphate in the body. Parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) control calcium homeostasis, whereas PTH, 1,25(OH)2D, and bone-derived fibroblast growth factor 23 (FGF 23) control phosphate homeostasis. Hypoparathyroidism can cause hypocalcemia and hyperphosphatemia, whereas deficient vitamin D actions can cause osteomalacia in adults and rickets in children. Hyperparathyroidism, alternatively, can cause hypercalcemia and hypophosphatemia. Laboratory tests of calcium, phosphate, PTH, and 25-hydroxyvitamin D are very useful in the diagnosis of abnormalities associated with calcium and/or phosphate metabolisms. Bone is constantly remodeled throughout life in response to mechanical stress and a need for calcium in extracellular fluids. Metabolic bone diseases such as osteoporosis, osteomalacia in adults or rickets in children, and renal osteodystrophy develop when bone resorption exceeds bone formation. Bone turnover markers (BTM) such as serum N-terminal propeptide of type I procollagen (P1NP) and C-terminal collagen cross-link (CTX) may be useful in predicting future fracture risk or monitoring the response to anti-resorptive therapy. There is a need to standardize sample collection protocols because certain BTMs exhibit large circadian variations and tend to be influenced by food intakes. In the United States, a project to standardize BTM sample collection protocols and to establish the reference intervals for serum P1NP and serum CTX is ongoing. We anticipate the outcome of this project to shine lights on the standardization of BTM assays, sample collection protocols, reference intervals in relation to age, sex, and ethnic origins, and clinical utilities of BTMs. This review will briefly discuss the regulations of calcium and phosphate homeostasis, laboratory's role in the diagnosis, and monitoring of bone and calcium metabolism, as well as the usefulness and controversies of the utilities of BTMs in the diagnosis and monitoring of metabolic bone diseases.

Heavy Cannabis Use Is Associated With Low Bone Mineral Density and an Increased Risk of Fractures

PurposeTo investigate possible associations between recreational cannabis use and bone health in humans. MethodsCross-sectional study of individuals recruited from primary care in the UK between 2011 and 2013. Cases were regular smokers of cannabis divided into moderate (n = 56) and heavy user (n = 144) subgroups depending on whether they reported fewer or more than 5000 cannabis smoking episodes during their lifetime. Controls comprised 114 cigarette smokers. ResultsHeavy cannabis users had lower total hip bone mineral density (mean ± SD Z-score: −0.20 ± 0.9 vs +0.2 ± 0.9, P < .0005), lower spine bone mineral density (−0.5 ± 1.2 vs 0.0 ± 1.2, P < .0005), and lower body mass index (BMI; 26.5 ± 6.0 vs 29.0 ± 7.0, P = .01) than controls. Fracture rate was also increased in heavy users (rate ratio = 2.17; 95% confidence interval, 1.59-2.95; P < .001). When compared with controls, serum cross-linked C-telopeptide of type 1 collagen (CTX) concentrations were raised in heavy cannabis users (0.3 ± 0.1 vs 0.2 ± 0.1 pg/mL, P = .045), as were serum N-terminal propeptide of type 1 procollagen (P1NP) concentrations (47.1 ± 19.2 vs 41.2 ± 17.8 pg/mL, P = .01). Serum total 25-hydroxyvitamin D concentrations were reduced in heavy users compared with controls (25.3 ± 16.8 vs 36.9 ± 26.7 nmol/L, P = .002). Multiple regression analysis revealed that heavy cannabis use was an independent predictor of spine bone mineral density, accounting for 5.4% of the variance (P = .035), and total hip bone mineral density, accounting for 5.8% of the variance (P = .001), but mediation analysis suggested that the effect on spine bone mineral density was indirect and mediated through low body mass index. ConclusionsHeavy cannabis use is associated with low bone mineral density, low BMI, high bone turnover, and an increased risk of fracture. Heavy cannabis use negatively impacts on bone health both directly and indirectly through an effect on BMI.

Effects of chronic sleep deprivation on bone mass and bone metabolism in rats.

BackgroundThis study aimed to assess the effects of chronic sleep deprivation (CSD) on bone mass and bone metabolism in rats.MethodsTwenty-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.ResultsCompared 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).ConclusionsCSD markedly affects bone health by decreasing BMD and 25(OH)D, deteriorating the bone microarchitecture, and decreasing bone formation and bone resorption markers.

Vitamin E homologues α- and γ-tocopherol are not associated with bone turnover markers or bone mineral density in peri-menopausal and post-menopausal women.

In a large cohort of older women, we investigated the relationships that different forms of vitamin E may have with bone turnover markers and bone mineral density (BMD). We found a suggestive positive association between serum alpha-tocopherol and BMD at the femoral neck, but no other clinically relevant observations. Vitamin E has anti-oxidant and anti-inflammatory properties hypothesized to benefit bone, but limited studies exist regarding its homologues. We examined circulating and dietary α- and γ-tocopherols with bone turnover markers (BTMs) and bone mineral density (BMD), and the role of inflammation in this relationship. We performed two cross-sectional analyses from two visits (V2, 1997-1999, n = 3883; V3, 2007-2011, n = 2130) of the Aberdeen Prospective Osteoporosis Screening Study. Dietary and supplement intakes by food frequency questionnaire were assessed at both visits. V2 BTMs (urinary free pyridinoline and deoxypyridinoline, serum N-terminal propeptide of type 1 collagen) and V3 serum α- and γ-tocopherols, inflammatory markers (interleukin-6 [IL-6], serum amyloid A [SAA], high-sensitivity C-reactive protein [hs-CRP], E-selectin) and dual X-ray absorptiometry BMD at the femoral neck and lumbar spine were collected. Food sources of tocopherol homologues and diet-serum correlations were determined. The relationships between dietary tocopherols and BTMs (V2), and dietary and serum tocopherols with BMD (V3) were examined by multivariable regression (adjusting for age, cholesterol, inflammatory markers, carotenoids, body mass index, physical activity level, alcohol intake, smoking status and national deprivation category). Serum γ-tocopherol was associated with increasing concentrations of hs-CRP, SAA and E-selectin (P-trend all <0.0001), while α-tocopherol was associated with decreasing concentrations of IL-6 and hs-CRP (P-trend all <0.001). Controlling for covariates, serum α-tocopherol was positively associated with BMD at the femoral neck (β = 0.002, P = 0.04) among those not reporting vitamin E supplementation. We did not find biologically meaningful results between dietary and tocopherol homologues with BTMs or BMD.

The relationship between bone mineral density and bone metabolic markers in patients with spine degeneration diseases needing surgery

Objective The aims of this study were to evaluate the morbidity of osteoporosis and the relationship between bone mineral density (BMD) and bone metabolic markers in the patients with spine degeneration disease needing surgery, at the same time to observe the influence of type 2 diabetes mellitus on bone metabolism and BMD. Methods This retrospective analysis included 139 patients suffered by spine degeneration disease needing surgery from the October 2013 to October 2014 in Beijing Jishuitan Hospital. Lumbar BMD was measured by quantitative computed tomography (QCT) before surgery. Serum N-terminal propeptide of type I procollagen (PINP) , β C-terminal cross-linked telopeptide of type I collagen (β-CTX), osteocalcin (OC) , 25-hydroxyvitamin D[25(OH)D], parathyroid hormone (PTH), calcium and phosphorus were quantified simultaneously. The relationship between the results of lumbar BMD measured by QCT and bone metabolic markers was analyzed by partial correlation. The differences of bone metabolic markers among three groups classified according to BMD were performed by one-way ANOVA and analysis of covariance. The influence factors of lumbar BMD measured by QCT were analyzed by multifactor linear regression. T-test was used to analyze the differences of BMD and bone metabolic markers between two groups with and without type 2 diabetes mellitus. Results The average age of 139 patients was(62.74±6.83) years old. Lumbar BMD revealed that the percentage of osteoporosis, osteopenia and normal BMD were 40.2% (56/139) , 43.8% (61/139) and 16% (22/139) separately. The percentage was 47% (66/139) in subjects with 25(OH)D below 30 nmol/L. The percentage of subjects with the concentrations of 25(OH)D between 30-50 nmol/L was 40% (55/139) , while the percentage of subjects with the concentrations of 25(OH)D between 50-125 nmol/L was only 13% (18/139). Partial correlation analysis revealed that lumbar BMD measured by QCT was negatively correlated with PINP (r=-0.352, P<0.01), β-CTX (r=-0.356, P<0.01) and OC (r=-0.276, P=0.001) with gender and type 2 diabetes mellitus as covariates. Along with the age of patients increasing and BMD reducing, the levels of PINP, β-CTX and OC increased gradually and the differences were statistically significant (F=11.575, P<0.01; F=11.550, P<0.01; F=9.738, P<0.01). Multiple linear regression analysis revealed that age and PINP were the main factors that influenced the change of BMD in the patients with spine degeneration disease needing surgery (β=-1.863, t=-5.425, P<0.01; β=-0.393, t=-2.061, P=0.041) . Subjects were divided into diabetes group and non-diabetes group according to the clinical diagnosis and whether having abnormal serum glucose. The levels of PINP (36.56±14.56 versus 49.51±16.68 μg/L) , β-CTX (0.39±0.20 versus 0.52±0.21 μg/L) and OC (14.21±5.13 versus 20.74±6.84 μg/L) in serum between two groups had significant differences (t=3.648, P<0.01; t=2.754, P<0.01; t=4.573, P<0.01) . Conclusions There was prevalence of osteoporosis, osteopenia and vitamin D deficiency in the patients with spine degeneration disease needing surgery. The patients with high level of PINP and age were more prone to appear lower BMD which increasing the risk of osteoporosis. The patients combined with type 2 diabetes mellitus had suppressed bone markers which maybe the risk factor, independent of BMD, increasing fracture risk.(Chin J Lab Med, 2016, 39: 267-271) Key words: Spinal diseases; Osteoporosis; Bone density; Diabetes mellitus, type 2; Retrospective studies

Potential Usefulness of BMD and Bone Turnover Monitoring of Zoledronic Acid Therapy Among Women With Osteoporosis: Secondary Analysis of Randomized Controlled Trial Data.

We aimed to compare the clinical validity and the detectability of response of short-term changes in bone mineral density (BMD; hip and spine) and bone turnover markers (serum PINP and CTX) through secondary analysis of trial data. We analyzed data on 7765 women with osteoporosis randomized to 5-mg once-yearly infusions of zoledronic acid or placebo in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT; trial ran from 2002 to 2006) and the first extension trial (trial ran from 2006 to 2009). We assessed the clinical validity and detectability of response for 1-year measurements of the following monitoring tests: total hip and lumbar spine BMD, serum N-terminal propeptide of type I collagen (sPINP), and serum C-telopeptide of type I collagen (sCTX; 6-month measurement used). Clinical validity was assessed by examining prediction of clinical fracture in Cox models; detectability of response to treatment was assessed by the ratio of signal to noise, estimated from the distributions of change in zoledronic acid and placebo groups. Baseline measurements were available for 7683 women with hip BMD, 558 with spine BMD, 1246 with sPINP, and 517 women with sCTX. Hip BMD and sPINP ranked highly for prediction of clinical fracture, whereas sPINP and sCTX ranked highly for detectability of response to treatment. Serum PINP had the highest overall ranking. In conclusion, serum PINP is potentially useful in monitoring response to zoledronic acid. Further research is needed to evaluate the effects of monitoring PINP on treatment decisions and other clinically relevant outcomes. © 2016 American Society for Bone and Mineral Research.

State of bone tissue in patients with thyrotoxicosis syndrome

Оbjective. To determine the influence of thyroid functional state on bone mineral density indexes from data of ultrasound densitometry and laboratory methods of research.Materials and methods. 80 patients of reproductive age with thyrotoxicosis syndrome were recruited. The thyroid functional state was estimated by means of determination of thyroid-stimulating hormone (TSH) basal concentrations and free thyroxine in the blood serum. Subjects were invited to attend quantitative ultrasound densitometry (Sahara), and a fasting blood sample from which osteocalcin, serum N-terminal propeptide of type 1 procollagen and crosslinks were also measured.Results. Frequency of bone mineral density disorders in patients with thyrotoxicosis syndrome was 52,7%, including osteopenia in 40% and osteoporosis in 12.7%. A basic factor that results in the decline of bone mineral density in patients with thyrotoxicosis syndrome is excessive products of thyroid hormones, and also TSH-suppressive doses of levothyroxine. Ultrasound densitometry showed significant decrease of bone mineral density indexes and increase of frequency of osteopenia and osteoporosis as compared to healthy persons.Conclusions. Complex approach is the first brought to the estimation of bone metabolism state in patients with thyrotoxicosis syndrome. It contains an ultrasound densitometry and laboratory methods of research. Set factors (excessive products of thyroid hormones, reception of preparations of thyroid hormones in TSH-suppressive doses) and mechanisms of negative influence (stimulation of osteoclastic activity, decline of osteoblastic activity) on the state of bone metabolism in patients with thyrotoxicosis syndrome.

Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model

Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.

Oxytocin and bone status in men: analysis of the MINOS cohort.

Oxytocin, a neurohypophysial hormone, regulates bone metabolism in animal studies and postmenopausal women. In men, oxytocin is not associated with bone mineral density, bone turnover markers, or prevalent fractures, but weakly negatively with incident fragility fracture requiring further studies. We previously showed that serum oxytocin (OT) level is associated with bone mineral density (BMD) and bone turnover rate in postmenopausal women. The aim of our study was to assess the relationship between circulating OT levels and bone status in men. In 552 men aged 50 and older from the MINOS cohort, we measured serum levels of OT. We assessed the association of serum OT levels with BMD (lumbar, femoral neck, total hip), bone turnover markers (BTM) (serum N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (bone ALP), and C-terminal telopeptide of type I collagen (CTX-I)) and fracture risk. In the univariate analysis, serum OT level was not associated with BMD at any site, BTM levels, or with prevalent or incident fracture. OT was significantly correlated with body mass index (BMI) (r = 0.17, p < 0.001), total or bioavalaible 17β-estradiol (r = 0.09, p = 0.04 and r = 0.20, p < 0.001, respectively), free testosterone (r = 0.17, p < 0.001), and leptin (r = 0.16, p < 0.001). Multivariate analysis did not show significant relationship between serum OT and BMD. After adjustment for age, BMI, interaction BMI/age, history of fall in the last year, and BMD, OT and prevalent fracture were not associated. By contrast, the same analysis with additional adjustment for prevalent fracture showed a weakly significant negative association between OT and incident fracture, e.g., after adjustment for femoral neck BMD, HR = 0.73, 95 %CI 0.55-0.99, p = 0.04. In men, serum OT levels are not associated with BMD, bone turnover rate, or prevalent fractures. The weak negative relationship with fracture risk requires further studies.

Risk factors for incisional hernia after hepatic resection for hepatocellular carcinoma in patients with liver cirrhosis

The risk factors for incisional hernia (IH) and the association between liver fibrosis and IH after hepatic resection in patients with hepatocellular carcinoma (HCC) with liver cirrhosis (LC) are still unclear. We aimed to evaluate the rate of IH and to assess the effect of perioperative factors, including serum markers for liver fibrosis, on the risk of IH. A total of 192 patients with HCC with LC who received hepatectomy were retrospectively analyzed. The primary end point was the incidence rate of IH and the secondary end points were associations between IH and 22 clinical factors. IH was diagnosed in 60 (31.3%) patients. The estimated incidence rates were 19.8% at 12 months, 32.5% at 36 months, and 38.8% at 60 months. In multivariable analysis, the presence of postoperative intractable ascites (odds ratio 24.83, P = .0003), abdominal wall closure by a single-layer mass closure with a continuous running suture (odds ratio 4.59, P = .0143), preoperative body mass index ≥ 25 kg/m(2) (odds ratio 3.36, P = .0025), and preoperative serum N-terminal pro-peptide of type IV collagen 7S domain (P4NP 7S) levels ≥ 5 ng/mL (odds ratio 3.13, P = .0234) were independent risk factors. There are several risk factors for IH after hepatic resection in HCC patients with LC. Preoperative serum P4NP 7S levels ≥ 5 ng/mL are a useful predictive marker, and abdominal wall closure with a continuous running suture by a single-layer mass closure should be avoided.