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Bone metabolism markers are associated with neck circumference in adult Arab women.
Albassam, RS, Sabico, S, Alnaami, AM, Khattak, MNK, Lei, KY, Al-Daghri, NM, Reginster, JY, Alokail, MS
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2019;(4):845-852
Abstract
UNLABELLED The study aimed to determine whether neck circumference is associated with bone metabolism markers among adult Arab women and found modest but significant associations with bone resorption markers, suggesting that neck circumference, a surrogate measure of upper subcutaneous fat, influences bone turnover expression among adult females. INTRODUCTION Body fat distribution is associated with decreased bone resorption and neck circumference (NC), a surrogate measure for upper body fat, has never been tested as a marker that can reflect bone turnover. This is the first study aimed to analyze the associations between NC and several bone biomarkers among adult Saudi women. METHODS This cross-sectional study included a total of 265 middle-aged Saudi women [86 non-obese (mean age 52.7 ± 8.1; mean BMI 26.9 ± 2.3) and 179 obese (mean age 50.6 ± 7.5; mean BMI 35.7 ± 4.5)] recruited from primary care centers in Riyadh, Saudi Arabia. Anthropometrics included BMI, NC, waist and hip circumferences, total body fat percentage (%), and blood pressure. Biochemical parameters included glucose and lipid profile which were measured routinely. Serum levels of 25(OH) D, parathyroid hormone, RANKl, sclerostin, C-terminal telopeptide of collagen I (CTX-I), Dkk1, IL1β, osteoprotegerin, osteopontin, and osteocalcin were measured using commercially available assays. RESULTS In all groups, NC was inversely associated with PTH (R = - 0.22; p < 0.05) and positively associated with osteoprotegerin (R = 0.20; p < 0.05) even after adjustments for age and BMI. Using all anthropometric indices as independent variables showed that only NC explained the variance perceived in CTX-I (p = 0.049). In the non-obese, waist-hip ratio (WHR) was significantly associated with sclerostin (R = 0.40; p < 0.05) and body fat was significantly associated with osteopontin (R = 0.42; p < 0.05). CONCLUSION NC is modestly but significantly associated with bone biomarkers, particularly the bone resorption markers, among adult Arab women. The present findings highlight the importance of NC as measure of upper body subcutaneous fat in influencing bone biomarker expression in adult females.
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Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men.
Pye, SR, Ward, KA, Cook, MJ, Laurent, MR, Gielen, E, Borghs, H, Adams, JE, Boonen, S, Vanderschueren, D, Wu, FC, et al
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2017;(3):935-944
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UNLABELLED Peripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40-79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline. INTRODUCTION This study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change. METHODS Men aged 40-79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (β-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later. RESULTS Five hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (-0.04 %/year), bone mineral content (BMC) (-0.1 %/year) and cortical thickness (-0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (-0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters. CONCLUSIONS Age-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.
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Greater change in bone turnover markers for efavirenz/emtricitabine/tenofovir disoproxil fumarate versus dolutegravir + abacavir/lamivudine in antiretroviral therapy-naive adults over 144 weeks.
Tebas, P, Kumar, P, Hicks, C, Granier, C, Wynne, B, Min, S, Pappa, K
AIDS (London, England). 2015;(18):2459-64
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OBJECTIVE Antiretroviral therapy initiation has been linked to bone mineral density and bone biomarker changes. We assessed long-term bone turnover biomarker effects over 144 weeks in patients initiating dolutegravir (DTG) + abacavir/lamivudine (ABC/3TC) versus efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). METHODS Patients randomized in SINGLE received DTG (50 mg once daily) + ABC/3TC or fixed-dose combination EFV/FTC/TDF. We evaluated vitamin D serum levels and bone turnover markers (BTMs), including type 1 collagen cross-linked C-telopeptide (CTx), osteocalcin, bone-specific alkaline phosphatase (BSAP), and procollagen type 1 N-terminal propeptide (P1NP), at baseline and weeks 48, 96, and 144. RESULTS Among the 833 enrolled patients (68% white, 85% men), baseline median age was 35 years (range 18-85), median CD4 was 338 cells/μl, and median BMI was 24 kg/m. Fifty-three percent of patients smoked, and 6% reported baseline vitamin D use, with no meaningful differences between groups. Relative to baseline, CTx, osteocalcin, BSAP, and P1NP increased; vitamin D decreased in both groups at weeks 48, 96, and 144. Changes from baseline typically peaked at weeks 48 or 96 and for the four analytes, excluding vitamin D, with the EFV/FTC/TDF group having significantly greater changes from baseline at all time points. CONCLUSION DTG + ABC/3TC in antiretroviral therapy-naive patients resulted in significantly lower increases in BTMs (CTx, osteocalcin, BSAP, P1NP) compared with EFV/FTC/TDF over 144 weeks. The observed changes are consistent with results from other smaller, randomized trials. These differences in BTMs likely correlate with changes in bone mineral density over time.
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Romosozumab in postmenopausal women with low bone mineral density.
McClung, MR, Grauer, A, Boonen, S, Bolognese, MA, Brown, JP, Diez-Perez, A, Langdahl, BL, Reginster, JY, Zanchetta, JR, Wasserman, SM, et al
The New England journal of medicine. 2014;(5):412-20
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BACKGROUND Sclerostin is an osteocyte-derived inhibitor of osteoblast activity. The monoclonal antibody romosozumab binds to sclerostin and increases bone formation. METHODS In a phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-group study, we evaluated the efficacy and safety of romosozumab over a 12-month period in 419 postmenopausal women, 55 to 85 years of age, who had low bone mineral density (a T score of -2.0 or less at the lumbar spine, total hip, or femoral neck and -3.5 or more at each of the three sites). Participants were randomly assigned to receive subcutaneous romosozumab monthly (at a dose of 70 mg, 140 mg, or 210 mg) or every 3 months (140 mg or 210 mg), subcutaneous placebo, or an open-label active comparator--oral alendronate (70 mg weekly) or subcutaneous teriparatide (20 μg daily). The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Secondary end points included percentage changes in bone mineral density at other sites and in markers of bone turnover. RESULTS All dose levels of romosozumab were associated with significant increases in bone mineral density at the lumbar spine, including an increase of 11.3% with the 210-mg monthly dose, as compared with a decrease of 0.1% with placebo and increases of 4.1% with alendronate and 7.1% with teriparatide. Romosozumab was also associated with large increases in bone mineral density at the total hip and femoral neck, as well as transitory increases in bone-formation markers and sustained decreases in a bone-resorption marker. Except for mild, generally nonrecurring injection-site reactions with romosozumab, adverse events were similar among groups. CONCLUSIONS In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).
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Profile of changes in bone turnover markers during once-weekly teriparatide administration for 24 weeks in postmenopausal women with osteoporosis.
Sugimoto, T, Nakamura, T, Nakamura, Y, Isogai, Y, Shiraki, M
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2014;(3):1173-80
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SUMMARY Changes in bone turnover markers with weekly 56.5 μg teriparatide injections for 24 weeks were investigated in women with osteoporosis. Changes in bone turnover markers 24 h after each injection of teriparatide were constant. During the 24 week period, bone formation markers increased and baseline bone resorption marker levels were maintained. INTRODUCTION This study aimed to clarify the changes in bone turnover markers during 24 weeks of once-weekly teriparatide injections in postmenopausal women with osteoporosis. METHODS The 24 h changes in pharmacokinetics (PK), calcium metabolism, and bone turnover markers (serum osteocalcin, procollagen type I N-terminal propeptide (P1NP), urinary cross-linked N-telopeptide of type I collagen (NTX), deoxypiridinoline (DPD)) after each injection of 56.5 μg teriparatide at the data collection weeks (0, 4, 12, and 24 weeks) were investigated. The changes were evaluated by comparison with the data at 0 h in each data collection week. RESULTS Similar 24 h changes in each parameter after injection of teriparatide were observed in each data collection week. Serum calcium increased transiently, and intact PTH decreased 4-8 h after injection; serum calcium subsequently returned to baseline levels. Calcium and intact PTH levels decreased for 24 weeks. Although serum osteocalcin decreased at 24 h, it was significantly increased at 4 weeks. P1NP decreased transiently and then increased significantly at 24 h. P1NP was significantly increased at 4 weeks. Urinary NTX and DPD were significantly increased transiently and then decreased at 24 h. The urinary DPD level decreased significantly at 4 weeks. CONCLUSIONS Twenty-four hour changes in PK, calcium metabolism, and bone turnover markers showed the same direction and level after once-weekly teriparatide injections for 24 weeks, with no attenuation of the effect over time. After 24 weeks, the bone formation marker, serum osteocalcin, increased significantly, but the serum P1NP, did not. Bone resorption markers decreased or remained the same.
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Effect of low-dose alendronate treatment on bone mineral density and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis.
Li, M, Zhang, ZL, Liao, EY, Chen, DC, Liu, J, Tao, TZ, Wu, W, Xia, WB, Lu, YJ, Sheng, ZF, et al
Menopause (New York, N.Y.). 2013;(1):72-8
Abstract
OBJECTIVE The aim of this study was to evaluate the effect of low-dose alendronate (ALN) treatment on bone mineral density (BMD) and bone turnover markers in Chinese postmenopausal women with osteopenia and osteoporosis. METHODS This study was a large-sample, randomized, open-label, prospective, multicenter, clinical trial with a 12-month follow-up. A total of 639 postmenopausal women (aged 62.2 ± 7.0 y) with osteopenia or osteoporosis were randomized into two groups: low-dose ALN (70 mg every two weeks) and standard-dose ALN (70 mg weekly). All patients were also supplemented with calcium (600 mg) and vitamin D3 (125 IU) daily. BMD (measured by dual-energy x-ray absorptiometry; Hologic and Lunar) and levels of serum bone turnover markers (bone resorption marker, carboxy-telopeptide of type I collagen; bone formation marker, alkaline phosphatase) were assessed at baseline and at 3, 6, and 12 months of treatment. BMD and bone turnover markers were compared between the baseline and the end of treatment, and the changes in BMD and bone turnover markers were also compared between the low-dose ALN group and the standard-dose ALN group. RESULTS No significant differences in age, years since menopause, body mass index, BMD, 25-hydroxy vitamin D level, and serum biochemical markers were found at baseline between the two dose groups. A total of 558 (87.3%) and 540 (84.5%) women completed the treatment at the 6th and 12th months, respectively. After the 12-month treatment, lumbar spine and hip BMD increased and serum bone turnover markers decreased significantly in both of the treatment groups (P < 0.01), and no differences in percentage changes in BMD at the lumbar spine, femoral neck, and hip were found between the low-dose group (5.60%, 3.87%, and 3.28%, respectively) and the standard-dose group (5.07%, 2.93%, and 3.80%, respectively; P > 0.05). However, levels of serum alkaline phosphatase and carboxy-telopeptide of type I collagen in the standard-dose group decreased moderately compared with those in the low-dose group (P < 0.05 and P < 0.01). The women tolerated the two doses of ALN quite well. Adverse effects were similar in the two groups. CONCLUSIONS Treatment with low-dose ALN (70 mg every two weeks) in women with postmenopausal osteopenia or osteoporosis effectively increases lumbar spine and hip BMD, similar to treatment with standard-dose ALN. Low-dose ALN may be a cost-effective and safe protocol for treating osteopenia or osteoporosis in Chinese women.
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The effect of PTH(1-84) or strontium ranelate on bone formation markers in postmenopausal women with primary osteoporosis: results of a randomized, open-label clinical trial.
Quesada-Gómez, JM, Muschitz, C, Gómez-Reino, J, Greisen, H, Andersen, HS, Dimai, HP
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;(9):2529-37
Abstract
UNLABELLED We explored the effects of PTH(1-84) compared with strontium ranelate on bone remodeling as measured by bone remodeling markers in postmenopausal women with osteoporosis. Biochemical markers of bone formation were significantly increased after treatment with PTH(1-84) but not strontium ranelate, indicating a different mechanism of action between these agents. INTRODUCTION PTH(1-84) and strontium ranelate (SR) are both known to reduce fracture risk in osteoporosis. Measuring changes in biochemical markers of bone turnover induced by these agents can help in characterizing the action of PTH(1-84) and SR on bone remodeling. METHODS A 24-week, randomized, open-label, parallel group, phase IV trial was conducted in 81 postmenopausal women with primary osteoporosis (≥50 years of age, lumbar spine, or total hip T-score ≤-2.5 SD) to assess the effect of SR as compared to PTH(1-84) on bone formation markers P1NP and BSAP. The bone resorption marker CTX was also measured. Subjects were randomly assigned to receive daily either 100 μg PTH(1-84) (n = 41) (subcutaneous injection) or oral 2 g SR (n = 40) for 24 weeks with daily supplements of 800 IU vitamin D(3) and 1,000 mg calcium. Patient-reported outcomes were collected to investigate the effect of treatment on quality of life (QoL). RESULTS Percentage changes from baseline in P1NP and BSAP were significantly increased for PTH(1-84) by week 24 compared with SR (p < 0.0001). Significant changes from baseline in P1NP and BSAP were noted for PTH(1-84) from week 4 onwards; no significant changes were noted for SR. A trend towards a positive impact on QoL was seen with PTH(1-84) treatment. Safety profiles concur with previous analyses. CONCLUSIONS PTH(1-84) had a more rapid and higher effect on bone formation markers compared to SR, indicating that SR has a different mode of action on bone remodeling than the bone building agent PTH(1-84) in postmenopausal women with osteoporosis.
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Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal Japanese women with osteoporosis.
Itabashi, A, Yoh, K, Chines, AA, Miki, T, Takada, M, Sato, H, Gorai, I, Sugimoto, T, Mizunuma, H, Ochi, H, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;(3):519-29
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This randomized, double-blind, placebo-controlled, dose-response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (-0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low-density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis.
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Metabolic profile of a continuous versus a cyclic low-dose combined oral contraceptive after one year of use.
Rad, M, Kluft, C, de Kam, ML, Meijer, P, Cohen, AF, Grubb, GS, Constantine, GD, Burggraaf, J
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception. 2011;(2):85-94
Abstract
OBJECTIVES To compare the effects of a combined oral contraceptive (COC) taken continuously with those of one of similar composition taken cyclically on 30 variables related to haemostasis, lipids, carbohydrates, bone metabolism, and sex hormone-binding globulin (SHBG). METHODS Randomised, open-label, multicentre, comparative substudy of a larger phase 3 trial involving 147 healthy women (age 18-49 years). Participants received the COC either continuously (levonorgestrel [LNG] 90 μg/ethinylestradiol [EE] 20 μg) or cyclically (21/7 days pattern; LNG 100 μg/EE 20 μg). RESULTS After 13 pill packs, changes in total cholesterol (+0.23 vs. -0.06 mmol/l), low-density lipoprotein cholesterol (+0.25 vs. -0.12 mmol/l), and high-density lipoprotein cholesterol(3) (-0.06 vs. -0.15 mmol/l) differed significantly (p<0.05) between the continuous and cyclic regimens, respectively. Increases were significantly greater (p <0.05) for protein C antigen (+11.8% vs. +6.1%) and SHBG (+791 vs. +565 nmol/l), and significantly smaller (p <0.05, ranks) for D-dimer (+19 vs. +37 μg FE/l). CONCLUSIONS Overall, the continuous and cyclic regimens affected metabolic variables similarly. The larger increase in SHBG with the continuous COC is consistent with a higher net oestrogenic effect due to a lower daily dose of LNG. Prospective studies are required to determine the long-term effects of this continuous COC regimen.
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Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent.
Cosman, F, Wermers, RA, Recknor, C, Mauck, KF, Xie, L, Glass, EV, Krege, JH
The Journal of clinical endocrinology and metabolism. 2009;(10):3772-80
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OBJECTIVE The aim of the study was to assess adding vs. switching to teriparatide 20 microg/d in patients on alendronate or raloxifene. DESIGN We conducted a randomized, open-label trial. PATIENTS AND INTERVENTIONS Postmenopausal women with osteoporosis on alendronate or raloxifene for at least 18 months added teriparatide (Add groups) or switched to teriparatide (Switch groups) for 18 months. MAIN OUTCOME MEASURES We measured bone turnover markers (BTM) and bone mineral density (BMD). RESULTS In the alendronate stratum, increases in BTM were smaller in the Add vs. Switch group [6-month PINP (64 vs. 401%); bone ALP (15 vs. 71%); betaCTX (27 vs. 250%); all P < 0.001]. However, at 6 months, total hip BMD increased more in the Add vs. Switch group (1.4 vs. -0.8%; P = 0.002). In the Add vs. Switch group, 18-month BMD increments were higher in lumbar spine (8.4 vs. 4.8%; P = 0.003) and total hip (3.2 vs. 0.9%; P = 0.02), but not in femoral neck (2.7 vs. 2.3%; P = 0.75). In the raloxifene stratum, increases in BTM were also smaller in the Add vs. Switch group [6-month PINP (131 vs. 259%; P < 0.001), bone ALP (31 vs. 44%; P = 0.035), and betaCTX (67 vs. 144%; P = 0.001)]. At 6 months, total hip BMD increase was greater in the Add vs. Switch group (1.8 vs. 0.5%; P = 0.028). At 18 months, increases in lumbar spine (9.2 vs. 8.1%), total hip (2.8 vs. 1.8%), and femoral neck (3.8 vs. 2.2%) were not significantly different between groups. CONCLUSIONS In women with osteoporosis treated with antiresorptives, greater bone turnover increases were achieved by switching to teriparatide, whereas greater BMD increases were achieved by adding teriparatide.