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1.
Bone resorption following weight loss surgery is associated with treatment procedure and changes in secreted Wnt antagonists.
Hofsø, D, Bollerslev, J, Sandbu, R, Jørgensen, A, Godang, K, Hjelmesæth, J, Ueland, T
Endocrine. 2016;(1):313-21
Abstract
To assess if altered bone turnover following bariatric surgery is related to metabolic consequences of the surgical procedure or weight loss. We evaluated serum markers reflecting bone turnover and metabolic pathways at baseline and after 1-year in a controlled non-randomized clinical trial comparing Roux-en-Y gastric bypass surgery (n = 74) with lifestyle intervention (n = 63) on obesity-related comorbidities. The decrease in body mass index (BMI) was larger in the surgery (-14.0 kg/m(2)) compared to lifestyle (-3.7 kg/m(2)). Markedly increased bone turnover was observed following surgery compared to lifestyle intervention and was correlated with change in BMI. Stepwise multivariable regression analysis revealed that group (β = 0.31, p < 0.01), and changes in BMI (β = -0.28, p < 0.01), dickkopf-1 (β = 0.20, p < 0.001) and sclerostin (β = 0.11, p < 0.05) were predictors of change in the bone resorption marker N-terminal telopeptide. Our data support that mechanisms related to the procedure itself and changes in secreted Wnt antagonists may contribute to increased bone turnover following bariatric surgery.
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Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women.
Binkley, N, Harke, J, Krueger, D, Engelke, J, Vallarta-Ast, N, Gemar, D, Checovich, M, Chappell, R, Suttie, J
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2009;(6):983-91
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Abstract
Low vitamin K status is associated with low BMD and increased fracture risk. Additionally, a specific menaquinone, menatetrenone (MK4), may reduce fracture risk. However, whether vitamin K plays a role in the skeletal health of North American women remains unclear. Moreover, various K vitamers (e.g., phylloquinone and MK4) may have differing skeletal effects. The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic, postmenopausal, North American women. In this double-blind, placebo-controlled study, 381 postmenopausal women received phylloquinone (1 mg daily), MK4 (45 mg daily), or placebo for 12 mo. All participants received daily calcium and vitamin D(3) supplementation. Serum bone-specific alkaline phosphatase (BSALP) and n-telopeptide of type 1 collagen (NTX) were measured at baseline and 1, 3, 6, and 12 mo. Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo. At baseline, the three treatment groups did not differ in demographics or study endpoints. Compliance with calcium, phylloquinone, and MK4 treatment was 93%, 93%, and 87%, respectively. Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX. No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed. This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal, North American women receiving calcium and vitamin D supplementation.
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Bone mineral density and bone turnover markers in patients receiving a single course of isotretinoin for nodulocystic acne.
Tekin, NS, Ozdolap, S, Sarikaya, S, Keskin, SI
International journal of dermatology. 2008;(6):622-5
Abstract
BACKGROUND High-dose isotretinoin has been reported to have adverse effects on bone mineral density (BMD); however, studies evaluating changes in BMD with isotretinoin therapy at different dosages and with varying treatment durations have produced conflicting results. OBJECTIVE To investigate the effect of a standard, single course of isotretinoin therapy on BMD and bone turnover markers in patients with nodulocystic acne. METHODS Thirty-six patients (15 male, 21 female) with severe, recalcitrant, nodulocystic acne and 36 healthy controls (16 male, 20 female) were enrolled in the study. Patients received isotretinoin treatment for 4-6 months until a cumulative dose of 120 mg/kg had been achieved. BMD in the lumbar spine and femur was measured at baseline and at the end of therapy by dual-energy X-ray absorptiometry. Serum calcium, phosphate, parathormone, total alkaline phosphatase, osteocalcin, free deoxypyridinoline, and urinary calcium were also measured before and at the end of treatment. RESULTS No significant differences were found in lumbar spine and femoral BMD between the patient and control groups at the beginning of the study (P > 0.05), and no statistically significant difference was observed between the BMD values in patients at the beginning vs. the end of treatment (P > 0.05). No statistically significant difference in bone turnover markers was found between patients and controls at the beginning of the study (P > 0.05), and no statistically significant changes in bone turnover markers were observed in patients at the beginning vs. the end of treatment (P > 0.05). CONCLUSION A single course of isotretinoin therapy has no clinically significant effect on bone metabolism.
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Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNF-alpha, TGF-beta1 and bone turnover markers in the treatment of postmenopausal osteoporosis.
Ozmen, B, Kirmaz, C, Aydin, K, Kafesciler, SO, Guclu, F, Hekimsoy, Z
European cytokine network. 2007;(3):148-53
Abstract
BACKGROUND Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-alpha and TGF-beta1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis. OBJECTIVE In this study, we evaluated the effects of raloxifene (Evista); Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-alpha and TGF-beta1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment. METHODS Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study. RESULTS It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-alpha and TGF-beta1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-beta1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-alpha levels in the patient group before and after treatment, were lower than those in the control group. CONCLUSION Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.
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The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial.
Herrmann, M, Umanskaya, N, Traber, L, Schmidt-Gayk, H, Menke, W, Lanzer, G, Lenhart, M, Peter Schmidt, J, Herrmann, W
Clinical chemistry and laboratory medicine. 2007;(12):1785-92
Abstract
BACKGROUND Hyperhomocysteinemia is a new risk factor for osteoporosis. This study analyzed the effect of a homocysteine (HCY)-lowering treatment in osteoporotic individuals. METHODS Osteoporotic subjects (n=47, 55-82 years) were treated with either a combination of 2.5 mg folate, 0.5 mg vitamin B(12) and 25 mg vitamin B(6) or placebo. Bone mineral density (BMD) at lumbar spine and hip was measured at baseline and after 1 year. Urinary desoxypyridinoline cross-links (DPD) and plasma levels of tartrate resistant acid phosphatase (TRAP), C-terminal cross-links of collagen I (CTx), pro-collagen type I N-terminal peptide (PINP) and osteocalcin (OC) were measured after 0, 4, 8 and 12 months. RESULTS B-vitamin supplementation significantly reduced HCY (0 vs. 12 months: 13.6+/-4.8 vs. 8.9+/-2.4 micromol/L). Placebo treatment had no effect on HCY (0 vs. 12 months: 12.0+/-3.4 vs. 12.7+/-3.9 micromol/L). BMD, TRAP, CTx, OC and PINP did not change throughout the study in both groups. Vitamin treatment decreased urinary DPD by -13% (p<0.01) after 8 and 12 months. In a sub-group analysis of hyperhomocysteinemic subjects (HCY>15 mumol/L, n=8), B-vitamin treatment tended to increase BMD at the lumbar spine, with a t-score from -2.7 to -1.7, and to decrease OC and PINP by approximately 50%. CONCLUSIONS B-vitamin supplementation had no consistent effects on bone turnover or BMD. However, the situation may be different in patients with hyperhomocysteinemia.
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The effect of a low-carbohydrate diet on bone turnover.
Carter, JD, Vasey, FB, Valeriano, J
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2006;(9):1398-403
Abstract
INTRODUCTION Low-carbohydrate diets have become popular as weight loss techniques. These diets are high in protein, saturated fats, and omega-6 fatty acids. They also lead to a ketogenic state. These factors could lead to increased bone turnover. This study was designed to see whether a low-carbohydrate diet would lead to increased bone turnover in humans. METHODS Thirty patients (15 study subjects and 15 controls) were recruited for this 3-month study. The 15 patients on the diet were instructed to consume less than 20 g of carbohydrates per day for the 1st month and then less than 40 g per day for months 2 and 3. Control subjects had no restrictions on their diet. The primary end point was urinary N-telopeptide (UNTx) at 3 months. Secondary end points included UNTx at 1 month, bone-specific alkaline phosphatase (BSAP) at 1 month, bone turnover ratio (BSAP/UNTx) at 1 month, and weight loss. RESULTS The mean UNTx in the study subjects increased by 1.6 [95% confidence interval (CI) +/-22.8] compared with an increase of 1.9 (95% CI +/-17.6) in the controls at 3 months (p=0.86). The mean UNTx decreased by 2.2 (95% CI +/-27.2) and 3.1 (95% CI +/-17.6) at 1 month in the dieters and controls, respectively (p=0.36). The mean BSAP decreased by 0.53 (95% CI +/-2.96) in the dieters and increased by 0.34 (95% CI +/-2.92) in the controls at 1 month (p=0.27). The bone turnover ratio increased by 0.08 (95% CI +/-0.81) in the dieters and by 0.05 (95% CI +/- 0.27) in the controls at 1 month (p=0.78). The dieters lost 6.39 kg versus 1.05 kg for the controls at 3 months (p=0.0008). CONCLUSIONS Although the patients on the low-carbohydrate diet did lose significantly more weight than the controls did, the diet did not increase bone turnover markers compared with controls at any time point. Further, there was no significant change in the bone turnover ratio compared with controls.
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Bone remodelling is not affected by consumption of a sodium-rich carbonated mineral water in healthy postmenopausal women.
Schoppen, S, Pérez-Granados, AM, Carbajal, A, de la Piedra, C, Pilar Vaquero, M
The British journal of nutrition. 2005;(3):339-44
Abstract
This study was designed to investigate the possible effects of consuming Na-rich carbonated mineral water on bone remodelling and urinary mineral excretion in postmenopausal women. Women (n 18) included were amenorrhoeic (>1 year), healthy and not obese (BMI <30 kg/m2). No woman was taking oestrogen replacement therapy, mineral and vitamin supplements, phyto-oestrogens or medications known to affect bone and lipid metabolism. In two consecutive interventions that lasted 8 weeks each, women drank 1 litre of control mineral water daily and 1 litre of carbonated mineral water, rich in Na, HCO3- and Cl-, daily. Body weight and height were measured, BMI was calculated and blood pressure was measured. Blood samples were taken from fasting subjects and serum obtained to analyse the biochemical bone markers, procollagen I amino-terminal propeptide (PINP) and beta-carboxy-terminal telopeptide of collagen (beta-CTX). At the end of each period, 24 h urine samples were collected to determine Ca, Mg, P, Na+, K+, Cl-, urine excretion and urinary pH. No changes in body weight, BMI or blood pressure were observed during the experimental period. Ca excretion was lower after the intake of carbonated water than after intake of the control water (P=0.037) while P excretion was higher (P=0.015). Total urine, Na and Cl- excretion did not differ between the two periods but urinary pH was increased after the intake of carbonated mineral water. PINP and beta-CTX did not differ between the two periods. Daily consumption of 1 litre of Na-rich carbonated mineral water for 8 weeks does not affect bone remodelling in healthy postmenopausal women.
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Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal.
Parkinson, C, Kassem, M, Heickendorff, L, Flyvbjerg, A, Trainer, PJ
The Journal of clinical endocrinology and metabolism. 2003;(12):5650-5
Abstract
Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 +/- 76 to 242 +/- 28 micro g/liter, P < 0.001) was associated with a significant decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated positively with the decrease of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there was no statistical difference between patients and controls for any parameters for which control data were available. In conclusion, GH excess is associated with increased bone and soft tissue turnover. Pegvisomant-induced normalization of serum IGF-I results in a decrease in markers of bone and soft tissue turnover to levels observed in age-matched controls, and these changes are accompanied by an increase in PTH and a decrease in 1,25-(OH)(2) vit D. These data provide further evidence of the effectiveness of pegvisomant in normalizing the altered biological effects of GH hypersecretion.
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The effects of three-month intravenous ibandronate on bone mineral density and bone remodeling in Klinefelter's syndrome: the influence of vitamin D deficiency and hormonal status.
Stepan, JJ, Burckhardt, P, Hána, V
Bone. 2003;(4):589-96
Abstract
The aim of this study was to evaluate the effects of a 2-year treatment with intravenous ibandronate (2 mg every 3 months) and calcium (1000 mg daily) on bone mineral density (BMD) and bone markers in 14 patients with Klinefelter's syndrome who served as their own controls. During the follow-up of 5.9 years before the treatment was started, the mean rates of bone loss per year were 1.3, 0.9, and 0.6% in the lumbar spine, femoral neck, and total body, respectively. The rate of bone loss from the spine was significantly inversely related to both serum estradiol and testosterone. At the onset of treatment, the average age of the patients was 55.2 years (48-64 years), and T score, mean +/- SD, at the lumbar spine was -2.6 +/- 1.0. After 6 months, the mean serum CTX and PINP decreased by 39 and 55% below the pretreatment concentrations, respectively (P < 0.05). After 12 months of treatment, the patients gained mean +/- SD, 7.8 +/- 2.3% of BMD in the lumbar spine, 3.8 +/- 4.0% in the femoral neck, and 4.7 +/- 2.2% in the total body (P < 0.05). During the second year of treatment, all patients also received 700 IU of vitamin D daily. After 24 months of treatment, the patients gained 10.1 +/- 4.3% of BMD in the lumbar spine, 6.7 +/- 5.5% in the femoral neck, and 5.5 +/- 2.5% in the total body. The increase in BMD in the second year of ibandronate treatment was not significant. The rate of gain of BMD in the femoral neck was positively related to serum concentrations of testosterone and inversely related to 25-hydroxyvitamin D (P < 0.005). After the discontinuation of treatment, serum CTX and PINP increased to the pretreatment levels, and the lumbar spine and femur neck BMD decreased (P < 0.05). In conclusion, ibandronate was effective in increasing BMD at all sites, but the effects were adversely influenced by vitamin D insufficiency or deficiency. The overall changes in biochemical markers of bone remodeling were consistent with the antiresorptive effect of the drug.
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Short-term risedronate treatment in postmenopausal women: effects on biochemical markers of bone turnover.
Raisz, L, Smith, JA, Trahiotis, M, Fall, P, Shoukri, K, Digennaro, J, Sacco-Gibson, N
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2000;(7):615-20
Abstract
The development of new biochemical markers has made it possible to assess the effects of therapeutic agents on bone turnover more rapidly and precisely. In this early phase II study, we analyzed the effects of short-term, high-dose treatment with risedronate, a potent pyridinyl bisphosphonate, on markers of bone resorption and formation. Resorption markers included urinary free deoxypyridinoline (D-Pyr) crosslinks, N-terminal telopeptide (NTx) and C-terminal telopeptide (CTx) type I collagen crosslinks. Bone formation markers included osteocalcin (OC), bone-specific alkaline phosphatase (BSAP) and the C-terminal peptide of type I procollagen (PICP). All three resorption markers showed rapid, significant (p<0.05) decreases from baseline following daily administration of 30 mg risedronate for 2 weeks. The mean decreases at 2 weeks were 28% for D-Pyr, 61% for NTx and 73% for CTx, respectively. Over the next 10 weeks after treatment, D-Pyr approached baseline while NTx and CTx remained well below baseline values. The markers of bone formation showed little change during therapy but decreased significantly at 4-10 weeks after therapy - an expected outcome of bisphosphonate therapy. Moreover, there was a significant correlation between the early effects on bone resorption markers and the delayed effects on formation markers. This study demonstrates that the approved dose of risedonate (30 mg/day) for Paget's disease is effective at decreasing bone turnover after 2 weeks of treatment, as observed by the sensitive response of bone turnover markers.