Sex-Specific Developmental ChangesBüyüme Sirasinda Cinsiyete Özgü Farkliliklar
Hogler W, Blimkie CJ, Cowell CT, Inglis D, Rauch F, Kemp AF, Wiebe P, Duncan CS, Farpour-Lambert N, Woodhead HJ Bone 2008;42:982-9
In 145 healthy subjects (6-25 years, 94 females). MRI and DXA were used to determine femur length, bone mineral content, cortical bone mineral density, bone diameter; cortical thickness; total, cortical and medullary areas; cross-sectional and polar moments of area; bone strength index and muscle area at the proximal one-third site of the femur. Results were dimensionally scaled by raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and 1/4, respectively. In prepubertal children, unscaled results expressed as percentages of adult values were lowest for variables with the highest dimensions (e.g., moments of area < bone mineral content < cross-sectional areas < femur length). However, when dimensionally scaled, results in children represented similar percentages of the respective average adult values. Before puberty, there was no sex difference in adjusted bone or muscle variables. After puberty, males had greater total and cortical bone area, bone diameter, moments of area, bone strength index and muscle area than women, both in absolute terms as well as adjusted for femur length and weight. The largest sex difference was found for muscle area. When compared relative to muscle size, young adult women attained greater total and cortical bone area than men. Postpubertal females have narrower femora, less bone strength and muscle size than males. However, when muscle size is taken into account, females have a larger femoral bone cross-section and more cortical bone.
Fracture Risk With Different Oral CorticosteroidsDegisik Oral Kortikosteroidlerle Iliskili Kirik RiskiVestergaard P, Rejnmark L, Mosekilde LCalcif Tissue Int 2008;82:249-57
Cases were all subjects with any fracture (655). For each case, three controls (962) matched on age and gender were randomly drawn from the population. Oral prednisolone/prednisone was associated with a dose-dependent increase in fracture risk starting from 6.7 mg/day. Oral budesonide was not associated with an increase in fracture risk, but the doses in were low (<3 mg/day). Oral hydrocortisone was not associated with risk of fractures. Oral methylprednisolone was only used intermittently and was not associated with an increase in overall fracture risk at the low doses used. After termination of oral prednisolone/prednisone, it took more than 1 year for fracture risk to return to background.
Glucocorticoid Excess Affects Cortical Bone Geometry in Premenopausal, But Not Postmenopausal, WomenGlukokortikoid Fazlaligi Sadece Premenopozal Kadinlarda Kortikal Kemik Geometrisini EtkilerKaji H, Yamauchi M, Chihara K, Sugimoto TCalcif Tissue Int 2008;82:182-90
Ninety-six women receiving oral GC and 10 women with Cushing syndrome (CS) were compared to controls using peripheral quantitative computed tomography. Total area, periosteal circumference, and polar strength strain index (SSIp) were lower in patients compared with control subjects in premenopausal women. Moreover, cortical area and thickness as well as periosteal circumference and SSIp were lower in patients with CS compared to controls in premenopausal women. Total area, cortical area, cortical thickness, periosteal circumference, as well as SSIp were lower in GC-treated patients with vertebral fractures compared to those without vertebral fractures in premenopausal women. In conclusion, endogenous or exogenous GC excess affects bone geometry of forearms of premenopausal, but not postmenopausal.
Impact of Glucose-Dependent Insulinotropic Peptide on Age-Induced Bone LossGlukoza Bagli Insulinotropik Peptidin Yasa Bagli Kemik Kaybina EtkisiDing KH, Shi XM, Zhong Q, Kang B, Xie D, Bollag WB, Bollag RJ, Hill W, Washington W, Mi QS, Insogna K, Chutkan N, Hamrick M, Isales CMJ Bone Miner Res 2008;23:536-43
Glucose-dependent insulinotropic peptide (GIP) is an enteric hormone whose receptors are present in osteoblasts, and GIP is known to stimulate osteoblastic activity in vitro. In vivo, GIP-overexpressing C57BL/6 transgenic (GIP Tg (+)) mice have increased bone mass compared with controls. Bone histomorphometric data suggest that GIP increases osteoblast number, possibly by preventing osteoblastic apoptosis. Changes in BMD, biomechanics, biomarkers of bone turnover, and bone histology were assessed in C57BL/6 GIP Tg(+) versus Tg(-) (littermate) mice between the ages of 1 and 24 mo of age. In addition, age-related changes in GIP receptor (GIPR) expression and GIP effects on differentiation of BMSCs were also assessed as potential causal factors in aging-induced bone loss. Bone mass and strength in GIP Tg(+) mice did not drop in a similar age-dependent fashion as in controls. GIP Tg (+) mice had increased osteoblastic activity compared with wildtype control mice. BMSCs express GIPR, that the expression decreases in an age-dependent manner, and that stimulation of BMSCs with GIP led to increased osteoblastic differentiation. Elevated GIP levels prevent age-related loss of bone mass and bone strength and suggest that age-related decreases in GIP receptor expression in BMSCs may play a role in this bone loss. Elevations in GIP may be an effective countermeasure to age-induced bone loss.
Development and Application of a Japanese Model of the WHO Fracture Risk Assessment Tool (FRAXTM)DSÖ’nün Kirik Riski Degerlendirme Yöntemi (FRAX TM)’nin Japon Modelinin Gelistirilmesi ve UygulanmasiFujiwara S, Nakamura T, Orimo H, Hosoi T, Gorai I, Oden A, Johansson H, Kanis JA Osteoporos Int 2008;19:429-35
To evaluate a Japanese version of FRAX, fracture probabilities were computed from published data on the fracture and death hazards in Japan. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. The 10-year probabilities of a major osteoporosis related fracture that corresponded to current intervention thresholds ranged from approximately 5% at the age of 50 years to more than 20% at the age of 80 years. The use of femoral neck BMD predicts fracture as well as or better than BMD tests at the lumbar spine.
Bazedoxifene in Postmenopausal WomenPostmenopozal Kadinlarda BazedoksifenSiris ES, Simon JA, Barton IP, McClung MR, Grauer AOsteoporos Int 2008;19:681-6
Postmenopausal women with osteopenia and no prevalent vertebral fractures were identified from BMD Multinational, BMD North America, VERT Multinational and VERT North America). 620 women with osteopenia were included, receiving either placebo (n=309) or risedronate 5 mg (n=311). Risedronate reduced the risk of fragility fractures by 73% over 3 years versus placebo (p=0.023); cumulative fragility fracture incidence was 6.9% in placebo-treated vs. 2.2% in risedronate-treated patients.
Adherence to Biphosphonates and Hip Fracture RiskBifosfonatlara Uyum ve Kalça Kirigi Riski
Rabenda V, Mertens R, Fabri V, Vanoverloop J, Sumkay F, Vannecke C, Deswaef A, Verpooten GA, Reginster JYOsteoporos Int 2008;19:811-8Compliance at 12 months was quantified using the medication possession ratio (MPR). Persistence was calculated as the number of days from the initial prescription to a gap of more than 5 weeks after completion of the previous refill. A logistic regression model was used to estimate the impact of compliance on the risk of hip fracture. The impact of persistence on hip fracture risk was analysed using the Cox proportional hazards model. The mean MPR at 12 months was higher among patients receiving weekly (n=15.021) compared to daily alendronate (136) (daily=58.6%; weekly=70.5%; p<0.001). At 12 months, the rate of persistence was 39.45%. For each decrease of the MPR by 1%, the risk of hip fractures increased by 0.4% (OR: 0.996:0.994-0.998). The relative risk reduction for hip fractures was 60% (HR: 0.404: 0.357-0.457) for persistent compared to nonpersistent patients. These results confirm that adherence to current therapeutic regimens remains suboptimal.
Alendronate and Atrial FibrillationAlendronat ve Atrial Fibrilasyon
Heckbert SR, Li G, Cummings SR, Smith NL, Psaty BMArch Intern Med 2008;168:826-31The HORIZON (Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly) trial reported a higher risk of serious atrial fibrillation (AF) in zoledronic acid recipients. In this study ever use of alendronate in a clinical practice setting identified 719 women with AF and 966 controls without AF. More AF case patients had ever used alendronate (6.5% [n=47] vs. 4.1% [n=40]; P=0.03), so ever use of alendronate was associated with a higher risk of incident AF (odds ratio, 1.86; 95%CI 1.09-3.15). The authors estimated that 3% of incident AF in this population might be explained by alendronate use.