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Intermittent zoledronic Acid prevents bone loss in adults after allogeneic hematopoietic cell transplantation.
Hari, P, DeFor, TE, Vesole, DH, Bredeson, CN, Burns, LJ
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2013;(9):1361-7
Abstract
Bone mineral density (BMD) loss is common in survivors of allogeneic hematopoietic cell transplantation (alloHCT). We performed a multicenter, phase II, randomized open-label trial of intravenous zoledronic acid (ZA) to prevent BMD loss in adult recipients of alloHCT with osteopenia before HCT. The treatment group received ZA 4 mg intravenously within 28 days pre-HCT and at 3 and 6 months after HCT. Both treatment and control groups received calcium carbonate and vitamin D supplements. Of 61 patients, 32 were randomized to the ZA cohort and 29 to the control cohorts. More patients in the ZA group had an HCT comorbidity index high-risk score of ≥3 (50% versus 21%, P < .01). Baseline BMD, T-scores, serum osteocalcin, bone alkaline phosphatase, and urine N-telopeptide (UNTX) levels were similar in both cohorts. Thirty patients were evaluable for outcomes (11 from the treatment and 19 from the control group). At 12 months, subjects in the treatment group had an improvement in BMD at the femoral neck (mean change, .018 for ZA group versus -.054 for controls; P = .04) and a significant decline in levels of UNTX (-56 for ZA group versus -9 for control; P = .04) compared with baseline. ZA was well tolerated and not associated with any cases of osteonecrosis of jaw or renal impairment. Lower survival observed in the ZA cohort was likely related to baseline imbalance in HCT-CI scores. Intermittent ZA is effective in preserving long-term bone health in adult alloHCT recipients at risk for osteoporosis.
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A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting markers of bone resorption or formation in postmenopausal women.
Cao, JJ, Johnson, LK, Hunt, JR
The Journal of nutrition. 2011;(3):391-7
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Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.
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Long-term cinacalcet HCl treatment improved bone metabolism in Japanese hemodialysis patients with secondary hyperparathyroidism.
Shigematsu, T, Akizawa, T, Uchida, E, Tsukamoto, Y, Iwasaki, M, Koshikawa, S, ,
American journal of nephrology. 2009;(3):230-6
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BACKGROUND/AIMS: Few clinical trials conducted with cinacalcet have thoroughly addressed its effects of on bone metabolism. We assessed the effects of cinacalcet on bone markers in Japanese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). METHODS 200 Japanese HD patients with intact PTH (iPTH) levels > or = 300 pg/ml were enrolled. The dose of cinacalcet was titrated from 25 up to 100 mg/day to achieve iPTH levels < or = 250 pg/ml for 52 weeks. RESULTS At the end of the study visit, 57.8% of patients (115/199) had achieved iPTH levels < or = 250 pg/ml. Serum Ca, phosphorus (P) and Ca x P levels decreased rapidly and were maintained throughout the study. At week 52, all bone metabolic markers levels had decreased significantly from baseline. Although bone resorption markers gradually decreased throughout the study period, bone alkaline phosphatase significantly increased during the first 4 weeks and then gradually decreased. CONCLUSIONS The time courses of changes in bone markers after cinacalcet treatment resembled those observed after surgical parathyroidectomy (PTx), sometimes described as the hungry bone syndrome, indicating that cinacalcet treatment induces a rapid recovery in bone response to calcium. In addition, long-term efficacy and safety of cinacalcet were also observed in Japanese patients undertaking long-term hemodialysis (167.0 +/- 81.4 months).
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Variable deficits of bone mineral despite chronic glucocorticoid therapy in pediatric patients with inflammatory diseases: a Glaser Pediatric Research Network study.
von Scheven, E, Gordon, CM, Wypij, D, Wertz, M, Gallagher, KT, Bachrach, L
Journal of pediatric endocrinology & metabolism : JPEM. 2006;(6):821-30
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OBJECTIVE To evaluate the relationship between chronic glucocorticoid (GC) exposure and bone mineral density (BMD) in children with rheumatic diseases and inflammatory bowel disease. STUDY DESIGN Lumbar spine BMD was measured by DXA in 86 GC-treated children (66% female, age 8-20 years, mixed ethnicity) screened for a multi-center intervention trial. Predictors of spine BMD z-score and vitamin D [25(OH)D] were examined by multivariable linear regression. RESULTS Mean prior year and lifetime cumulative GC exposure was 77.8 mg/kg and 224.6 mg/kg, respectively. BMD z-scores ranged from -3.7 to 2.2 SD (-1.1 +/- 1.2, mean +/- SD). Lower BMD z-scores were associated with increased prior year average daily GC dose (p = 0.03), decreased height z-score (p = 0.003), and decreased 25(OH)D concentrations (p = 0.03), but explained only a small proportion of BMD variability (adjusted R2 = 0.29). The 25(OH)D levels were <20 ng/ml in 45% of patients, and low 25(OH)D was associated with non-Caucasian ethnicity (p <0.001), increased age (p = 0.004), increased parathyroid hormone (p = 0.03), and residing in the Boston area (p <0.001). CONCLUSIONS Although GC exposure is significantly associated with BMD z-score, the association is too variable to serve as a consistent predictor of reduced BMD in children. Vitamin D insufficiency is common and may contribute to skeletal deficits in this population.
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A high dairy protein, high-calcium diet minimizes bone turnover in overweight adults during weight loss.
Bowen, J, Noakes, M, Clifton, PM
The Journal of nutrition. 2004;(3):568-73
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Weight loss induces bone resorption and this can be attenuated by calcium supplementation. Protein-rich diets were recently associated with favorable effects on bone density, although this remains controversial. We hypothesized that a diet high in calcium and protein would minimize bone resorption during weight loss compared with a lower calcium, protein-rich diet. The effects of dietary calcium in high protein diets on calcium excretion and bone metabolism were examined in overweight adults (n = 50, BMI 33.4 +/- 2.1 kg/m(2)) during 12 wk of energy restriction followed by 4 wk of energy balance. Subjects were randomly assigned to isoenergetic diets (5.5 MJ/d, 34% energy from protein, 41% carbohydrate, 24% fat) high in either dairy protein (DP, 2400 mg Ca/d) or mixed protein sources (MP, 500 mg Ca/d). During energy restriction, weight loss was 10% (-9.7 +/- 3.8 kg, P < 0.01), and 24-h urinary calcium excretion decreased independently of diet (-1.09 +/- 0.23 mmol/d, P < 0.01). By wk 16, the MP diet group had a 40% greater increase in deoxypyridinoline (bone resorption marker) than the DP diet group (P = 0.008). Osteocalcin (bone formation marker) increased from wk 0 to 16 in only the MP diet group [+2.16 +/- 0.63 micro g/L (+0.63 +/- 0.11nmol/L), P = 0.001]. In conclusion, weight loss was associated with increased bone resorption, yet the DP diet had a modest advantage over the MP diet by minimizing overall turnover. Combined with reduced urinary calcium excretion, this suggests that a high-protein, calcium-replete diet may protect against bone loss during weight reduction.
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Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation.
Shane, E, Addesso, V, Namerow, PB, McMahon, DJ, Lo, SH, Staron, RB, Zucker, M, Pardi, S, Maybaum, S, Mancini, D
The New England journal of medicine. 2004;(8):767-76
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BACKGROUND Osteoporosis is a well-known complication of cardiac transplantation. We conducted a randomized trial comparing alendronate with calcitriol for the prevention of bone loss during the first year after cardiac transplantation. METHODS A total of 149 patients were randomly assigned to receive either alendronate (10 mg per day) or calcitriol (0.5 microg per day) a mean (+/-SD) of 21+/-11 days after transplantation. Estimates of bone loss and the incidence of fractures among untreated patients were obtained from a reference group of 27 prospectively recruited patients who received cardiac transplants within the same period as the intervention groups. RESULTS At one year, the bone mineral density at the lumbar spine had decreased by a mean of 0.7 percent in the alendronate group and 1.6 percent in the calcitriol group (P=0.25 for the test of no difference). The bone mineral density at the femoral neck decreased by a mean of 1.7 percent in the alendronate group and 2.1 percent in the calcitriol group (P=0.69). In the reference group, the mean bone mineral density at the lumbar spine decreased by 3.2 percent (P=0.03 for the comparison with the alendronate group; P=0.15 for the comparison with the calcitriol group), and the mean density at the femoral neck decreased by 6.2 percent (P=0.001 for comparisons with both intervention groups). The incidence of vertebral fractures did not differ significantly among the groups (6.8 percent in the alendronate group, 3.6 percent in the calcitriol group, and 13.6 percent in the reference group). Hypercalciuria developed in 27 percent of the patients in the calcitriol group and 7 percent of those in the alendronate group (P=0.01). CONCLUSIONS The degree of bone loss and the rates of fracture did not differ significantly between the intervention groups. Calcitriol was associated with a higher risk of hypercalciuria. Alendronate-treated patients sustained less bone loss at the spine than those in the reference group, and both intervention groups sustained less bone loss at the hip than the reference group. The requirement for monitoring the serum and urinary calcium levels in calcitriol-treated patients makes alendronate more attractive for the prevention of bone loss early after cardiac transplantation.
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Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.
Eastell, R, Barton, I, Hannon, RA, Chines, A, Garnero, P, Delmas, PD
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2003;(6):1051-6
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Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.
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Bone resorption is induced on the second day of bed rest: results of a controlled crossover trial.
Baecker, N, Tomic, A, Mika, C, Gotzmann, A, Platen, P, Gerzer, R, Heer, M
Journal of applied physiology (Bethesda, Md. : 1985). 2003;(3):977-82
Abstract
The aim of the study was to analyze the kinetics of short-term changes in bone turnover. We studied in a randomized crossover design the effects of 6 days of bed rest on eight healthy male subjects (mean body wt: 70.1 +/- 5.7 kg; mean age: 25.5 +/- 2.9 yr). The metabolic ward period was divided into three parts: 4 ambulatory days, 6 days of either bed rest or non-bed rest periods, and 1 recovery day. The diet was identical in both bed rest and non-bed rest phases. Continuous urine collection started on the first day in the metabolic ward to analyze excretion of bone resorption markers, namely C-telopeptide (CTX) and N-telopeptide (NTX), creatinine, urea, and 3-methylhistidine. On the second ambulatory day and on the fifth day of bed rest or during the non-bed rest phase, blood was drawn to analyze bone formation markers and amino acid concentrations. Urinary calcium excretion was increased as early as the first day of bed rest (P < 0.01). CTX and NTX excretion stayed unchanged during the first 24 h of bed rest compared with the non-bed rest period. However, already on the second day, both resorption markers had increased significantly. NTX excretion increased by 28.7 +/- 14.0% (P < 0.01), whereas CTX excretion rose by 17.8 +/- 8.3% (P < 0.001). Creatinine, urea, and 3-methylhistidine excretion did not change. We conclude that 24 h of bed rest are sufficient to induce a significant rise in osteoclast activity in healthy subjects.
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Milk basic protein promotes bone formation and suppresses bone resorption in healthy adult men.
Toba, Y, Takada, Y, Matsuoka, Y, Morita, Y, Motouri, M, Hirai, T, Suguri, T, Aoe, S, Kawakami, H, Kumegawa, M, et al
Bioscience, biotechnology, and biochemistry. 2001;(6):1353-7
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Milk contains several components effective for bone health. In the previous in vitro and in vivo studies, we have shown that milk whey protein, especially its basic protein fraction (milk basic protein [MBP]), promoted bone formation and suppressed bone resorption. This present study examines the effect of MBP on the biochemical markers of bone metabolism in healthy adult men. Experimental beverages containing MBP (300 mg of MBP a day) were given to 30 normal healthy adult men for 16 days. The serum osteocalcin concentration had increased significantly after 16 days of ingesting the experimental beverage containing MBP. Urinary cross-linked N-teleopeptides of type-I collagen (NTx) excretion had decreased significantly after 16 days of ingesting MBP. The urinary NTx excretion was related to the serum osteocalcin concentration after 16 days of ingestion. These results suggest that MBP promoted bone formation and suppressed bone resorption, while maintaining the balance of bone remodeling.