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Bone histomorphometry before and after long-term treatment with cinacalcet in dialysis patients with secondary hyperparathyroidism.
Behets, GJ, Spasovski, G, Sterling, LR, Goodman, WG, Spiegel, DM, De Broe, ME, D'Haese, PC
Kidney international. 2015;(4):846-56
Abstract
The multicenter, single-arm BONAFIDE study characterized the skeletal response to cinacalcet in adult dialysis patients with plasma parathyroid hormone (PTH) levels of 300 pg/ml or more, serum calcium of 8.4 mg/dl or more, bone-specific alkaline phosphatase over 20.9 ng/ml and biopsy-proven high-turnover bone disease. Of 110 enrolled patients, 77 underwent a second bone biopsy with quantitative histomorphometry after 6-12 months of cinacalcet treatment. The median PTH decreased from 985 pg/ml at baseline to 480 pg/ml at the end of study (weeks 44-52). Bone formation rate/tissue area decreased from 728 to 336 μm(2)/mm(2)/day, osteoblast perimeter/osteoid perimeter decreased from 17.4 to 13.9%, and eroded perimeter/bone perimeter decreased from 12.7 to 8.3%. The number of patients with normal bone histology increased from none at baseline to 20 at 12 months. Two patients had adynamic bone at the end of study with a PTH under 150 pg/ml, and one patient with overt hypophosphatemia at baseline that reoccurred during follow-up developed osteomalacia. Thus, long-term treatment with cinacalcet substantially reduced PTH, diminished the elevated bone formation rate/tissue area, lowered several biochemical markers of high-turnover bone disease toward normal, and generally improved bone histology. Twenty patients had normal bone histology at follow-up, whereas most had mild hyperparathyroidism or mixed uremic osteodystrophy.
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Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin.
Ljunggren, Ö, Bolinder, J, Johansson, L, Wilding, J, Langkilde, AM, Sjöström, CD, Sugg, J, Parikh, S
Diabetes, obesity & metabolism. 2012;(11):990-9
Abstract
AIMS: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment. METHODS This international, multi-centre, randomized, parallel-group, double-blind, placebo-controlled study (ClinicalTrials.gov NCT00855166) enrolled patients with T2DM (women 55-75 years and men 30-75 years; HbA1c 6.5-8.5%; BMI ≥ 25 kg/m(2) ; body weight ≤ 120 kg) whose T2DM was inadequately controlled on metformin. One hundred and eighty-two patients were randomly assigned 1:1 to receive dapagliflozin 10 mg/day or placebo added to open-label metformin for a 24-week double-blind treatment period followed by a 78-week site- and patient-blinded extension period. At week 50, serum markers of bone formation (procollagen type 1 N-terminal propeptide; P1NP) and resorption (C-terminal cross-linking telopeptides of type I collagen; CTX), bone mineral density (BMD) as assessed by standardized Dual-Energy X-ray Absorptiometry (DXA) measurements and adverse events of fracture were evaluated as safety objectives. RESULTS One hundred and sixty-five patients (90.7%) completed the first 50 weeks. Compared with placebo, no significant changes from baseline in P1NP, CTX or BMD were identified over 50 weeks of dapagliflozin treatment, with no significant treatment-by-gender interactions. No fractures were reported. CONCLUSIONS Dapagliflozin had no effect on markers of bone formation and resorption or BMD after 50 weeks of treatment in both male and post-menopausal female patients whose T2DM was inadequately controlled on metformin.
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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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Maxillary sinus grafting with Bio-Oss or Straumann Bone Ceramic: histomorphometric results from a randomized controlled multicenter clinical trial.
Cordaro, L, Bosshardt, DD, Palattella, P, Rao, W, Serino, G, Chiapasco, M
Clinical oral implants research. 2008;(8):796-803
Abstract
INTRODUCTION This investigation was designed to compare the histomorphometric results from sinus floor augmentation with anorganic bovine bone (ABB) and a new biphasic calcium phosphate, Straumann Bone Ceramic (BCP). MATERIALS AND METHODS Forty-eight maxillary sinuses were treated in 37 patients. Residual bone width was > or =6 mm and height was > or =3 mm and <8 mm. Lateral sinus augmentation was used, with grafting using either ABB (control group; 23 sinuses) or BCP (test group; 25 sinuses); sites were randomly assigned to the control or test groups. After 180-240 days of healing, implant sites were created and biopsies taken for histological and histomorphometric analyses. The parameters assessed were (1) area fraction of new bone, soft tissue, and graft substitute material in the grafted region; (2) area fraction of bone and soft tissue components in the residual alveolar ridge compartment; and (3) the percentage of surface contact between the graft substitute material and new bone. RESULTS Measurable biopsies were available from 56% of the test and 81.8% of the control sites. Histology showed close contact between new bone and graft particles for both groups, with no significant differences in the amount of mineralized bone (21.6+/-10.0% for BCP vs. 19.8+/-7.9% for ABB; P=0.53) in the biopsy treatment compartment of test and control site. The bone-to-graft contact was found to be significantly greater for ABB (48.2+/-12.9% vs. 34.0+/-14.0% for BCP). Significantly less remaining percentage of graft substitute material was found in the BCP group (26.6+/-5.2% vs. 37.7+/-8.5% for ABB; P=0.001), with more soft tissue components (46.4+/-7.7% vs. 40.4+/-7.3% for ABB; P=0.07). However, the amount of soft tissue components for both groups was found not to be greater than in the residual alveolar ridge. DISCUSSION Both ABB and BCP produced similar amounts of newly formed bone, with similar histologic appearance, indicating that both materials are suitable for sinus augmentation for the placement of dental implants. The potential clinical relevance of more soft tissue components and different resorption characteristics of BCP requires further investigation.
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Impact of curriculum-based bone loading and nutrition education program on bone accrual in children.
Nichols, DL, Sanborn, CF, Essery, EV, Clark, RA, Letendre, JD
Pediatric exercise science. 2008;(4):411-25
Abstract
The purpose of this study was to investigate the influence of jumping activities and nutrition education on bone accretion in prepubescents. Fourth-grade children were divided into four groups: jumping (n = 61), nutrition (n = 9), jumping plus nutrition (n = 14), and control (n = 28). Interventions spanned the fourth and fifth grade academic years. Assessments were gathered at 0, 8 and 20 months. Baseline BMD values were (mean +/- SD): lumbar (0.752 +/- 0.095 g/cm2), neck (0.794 +/- 0.089 g/cm2) and total (0.907 +/- 0.060 g/cm2). There was a significant increase in BMD over time. However, the interventions produced no significant effects. Twice weekly jumping and/or biweekly nutrition education did not influence bone accrual.
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Early changes in biochemical markers of bone formation correlate with improvements in bone structure during teriparatide therapy.
Dobnig, H, Sipos, A, Jiang, Y, Fahrleitner-Pammer, A, Ste-Marie, LG, Gallagher, JC, Pavo, I, Wang, J, Eriksen, EF
The Journal of clinical endocrinology and metabolism. 2005;(7):3970-7
Abstract
CONTEXT Biochemical markers of bone turnover may reflect bone structure during anabolic treatment. OBJECTIVE The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment. DESIGN This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset. SETTING The trial was conducted at 11 clinical study sites. PATIENTS Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study. INTERVENTIONS Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered. MAIN OUTCOME MEASURES The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months. RESULTS U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters. CONCLUSIONS Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.