Functional outcome after hip fracture in elderly women is positively associated with circulating levels of insulin-like growth factor-I

Abstracts / Bone 44 (2009) S339–S450

hormone 140 pg/ml (95% Cl 85; 310); Са2+ 1.24 mmol/l (95%Cl 1,17; 1.44). 36 women with normal parathormone and Ca2+ levels were included into control group. There were no differences found in age, body mass index, and blood pressure level between asymptomatic group and control group. Women with symptomatic pHPT were significantly older (60 (90%Cl 31; 72) years) than women with asymptomatic pHPT (54(90%Cl 38; 70) years) and had longer duration of underlying disease and severe hypertension. Valvular and coronary heart diseases were excluded. Ambulatory blood pressure monitoring, echocardiography were performed in all patients. Results: Daily average systolic and diastolic blood pressures were similar in all groups. LVH was found in 56% of patients with symptomatic and in 32.4% of patients with asymptomatic pHPT (p = 0.0093). Left ventricular (LV) mass index, LV mass, interventricular septal thickness and LV posterior wall thickness were significantly higher in the former group of patients. In patients with pHPT and normal blood pressure LVH was significantly higher in those with more severe disease (46.1% and 12.5%, respectively, p = 0.06). Similar tendency was observed in subgroup with hypertension. LVH was revealed more frequently in patients with asymptomatic pHPT than in control group (32.4% and 28.6%, respectively), but the difference was not significant. Positive correlation was found between the parathormone level and interventricular septal thickness, LV posterior wall thickness, LV mass index and LV mass. Multiple regression analysis showed that both parathormone level (beta = 0.26), daily average systolic blood pressure (beta = 0.42), and hypertension (beta = 0.29) significantly independently influence on interventricular septal thickness. Conclusion: Persistent high level of parathormone contributes to the development of LVH, so it disturbs cardiovascular function. The rate of LVH in symptomatic pHPT is higher than in patients with asymptomatic pHPT, not only due to the higher blood pressure but also as a result of significant excess of parathormone and longer duration of disease in former group. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.195

P284 Calcium load attenuates the acute effect of teriparatide on serum beta-CTX in healthy men I. Raskaa,*, V. Zikana, J. Stepanb a Department of Internal Medicine 3, Charles University, Faculty of Medicine 1, Prague 2, Czech Republic b Institute of Rheumatology, Charles University, Faculty of Medicine 1, Prague 2, Czech Republic Background: A single-dose teriparatide injection in healthy men resulted in an acute increase of the serum cross-linked C-telopeptide of type I collagen (beta-CTX). The acute effect of teriparatide on betaCTX can be blocked by co-administration of salmon calcitonin (Raska et al. ECTS Symposium, 2008). The objective of the present study was to test the hypothesis that antiresorptive effect of the morning oral calcium load is able to modify the acute teriparatide action on serum beta-CTX. Methods: Six healthy men were each studied twice. Blood samples were obtained 3 h after a standard breakfast, prior to (baseline) and 30, 60, 90 and 120 min after a single subcutaneous administration of teriparatide (20 μg) with and without a simultaneous administration of oral calcium load (1000 mg). Results: The teriparatide alone resulted in a significant increase in serum beta-CTX with maximum mean increase of 83% at 120 min. When 1000 mg of calcium was co-administered with teriparatide, increase in beta CTX was significantly attenuated (maximum mean increase by 24% at 120 min). In conclusion, the present data in

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healthy men indicate that timing of oral calcium load can significantly affect the acute effect of teriparatide on bone resorption marker betaCTX. Whether long-term coadministration of calcium load with teriparatide might contribute to or attenuate the anabolic effect of teriparatide on bone requires further study. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.196

P285 Effect of Cinacalcet HCl and Maxacalcitol combination therapy for secondary hyperparathyroidism in chronic hemodialysis patients K. Saitoa,*, Y. Kimurab, H. Satoa, M. Onoc, Y. Ohtac, H. Ogawac a Nephrology, Tokai Clinic, Tokai, Japan b Nephrology, Kanayama Clinic, Japan c Nephrology, Shinseikai Daiichi Hospital, Nagoya, Japan Background: Cinacalcet HCl, a calcimimetic, and Maxacalcitol, a vitamin D analogue, are used to treat secondary hyperparathyroidism of chronic renal failure. Cinacalcet have an effect that decreases serum Ca level, thus it is possible to increase the dose of Maxacalcitol avoiding hypercalcaemia. Methods: We administrated Maxacalcitol for chronic hemodialysis patients, having secondary hyperparathyroidism, and then Cinacalcet additionally (n = 16). We examined Serum Ca, Pi, ALP, intact-PTH, ALB, before and after administration of Cinacalcet, until 8 months. Results: Mean administrated Cinacalcet dose is 28.4 +− 8.6 mg [Mean +− SD]. After Cinacalcet administration, Maxacalcitol administrated dose increased from 7.5 +− 6.2 μg/hemodialysis to 13.9 + − 10.3 μg/hemodialysis(p < 0.01) intact PTH decreased from 313 + − 88 pg/ml to 153 +− 61 pg/ml (4 w after), 91 +− 48 pg/ml (16 w after) (both p < 0.001). Serum Ca, Pi, ALP, ALB are n.s. Considerations: Maxacalcitol increases serum Ca level weakly, sometimes highly, so that the dose was administrated always insufficiently. Cinacalcet diminishes Ca load, and we administrated more Maxacalcitol, thus intact PTH decreased effectively. Conclusion: Cinacalcet HCl and Maxacalcitol combination therapy is suggested as effective for secondary hyperparathyroidism in chronic hemodialysis patients. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.197

P286 Abstract withdrawn doi:10.1016/j.bone.2009.03.198

P287 Functional outcome after hip fracture in elderly women is positively associated with circulating levels of insulin-like growth factor-I M. Di Monacoa,*, F. Valleroa, R. Di Monacob, R. Tapperoc, A. Cavannaa a Osteoporosis Research Center, Presidio Sanitario San Camillo, Italy b S.R.F., Società Ricerca e Formazione, Italy c Division of Physical Medicine and Rehabilitation, Presidio Sanitario San Camillo, Torino, Italy Insulin-Like Growth Factor-I (IGF-I) exerts potent anabolic actions in several tissues, including the muscle and the bone. Both older age and nutritional deficiencies are associated with low IGF-I levels, that

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can contribute to generate the catabolic changes accompanying aging and malnutrition. Elderly persons who sustain a fracture of the hip are often malnourished and commonly develop functional dependence in activities of daily living. Our aim was to investigate the association between IGF-I serum levels and functional outcome in hip-fracture women. We investigated 171 of 188 women admitted consecutively to our rehabilitation hospital after hip fracture. IGF-I serum levels were assessed by using an automated chemiluminescence immunoassay 21.3 ± 6.1 days (mean ± SD) after fracture occurrence. Functional outcome was assessed using Barthel Index scores. At a Spearman rank test we observed a significant positive correlation between IGF-I levels and both Barthel Index scores at discharge from in-patient rehabilitation (r = 0.213; p = 0.005) and changes in Barthel Index scores during rehabilitation (r = 0.222; p = 0.004). At multiple regression, a significant association between IGF-I and both functional scores and their changes during rehabilitation was found after adjustment for several potential confounders, including age, cognitive impairment, pressure ulcers, neurologic impairment, infections, Barthel index score at admission to rehabilitation, and length of stay in hospital (p < 0.05). Overall, the panel of prognostic factors accounted for 55% of the variance in the functional score and 31% of the variance in its change during rehabilitation. Data shows that IGF-I serum levels were positively associated with both Barthel index scores at the end of in-patient rehabilitation and the changes in the functional score during rehabilitation. Conflict of interest: This study was funded in part by Regione Piemonte, Ricerca Sanitaria Finalizzata.

examine the correlation between the two methods. Serum intact PTH levels were measured in all participants. Balance function was estimated with one-leg-stand test (OLST) and get-up-and-go test (GUAG) in all participants that were eligible. The mean serum 25(OH)D level was 20.3 ng/mL and mean iPTH level was 41.1 pg/mL. Serum 25(OH)D level of 30 ng/mL with the RIA method corresponded to 24.34 ng/mL with the CLIA method. Hence a cutoff level of 24.34 ng/mL was used to define vitamin D inadequacy. Vitamin D inadequacy was present in 242 (82.9%) men and in 486 (98.0%) women. There was a positive correlation between serum 25 (OH)D levels and BMD values at the lumbar spine, total femur and femur neck in women (p < 0.05, adjusted for age, BMI and waist circumference); however, in men, only total femur and femur neck BMD values were positively correlated with serum 25(OH)D levels (p < 0.05). Balance function test results had no significant correlations with serum 25(OH)D levels in women; only OLST results had positive correlations with serum 25(OH)D levels in men (P < 0.05). There was a high prevalence of vitamin D inadequacy in the province of Chungju. 25(OH)D levels were positively correlated with BMD values in both genders, and only OLST results had positive correlations with serum 25(OH)D levels in men. In general serum 25 (OH)D levels were associated with both bone health and muscle balance. More results from the ongoing Chungju Metabolic Disease Cohort Study need to analyzed. Conflict of interest: None declared. doi:10.1016/j.bone.2009.03.200

doi:10.1016/j.bone.2009.03.199

P288 Prevalence of vitamin D inadequacy in the province of Chungju, Korea: A population-based study M. Kanga,*, G. Kima, M. Kima, S. Leeb, K. Ohc, H. Chungd, D. Byune, H. Parkf a Department of Endocrinology and Metabolism, Yoido St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea b Department of Endocrinology and Metabolism, Holy Family Hospital, Bucheon, South Korea c Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University, South Korea d Department of Endocrinology and Metabolism, East-West Neo Medical Center, Kyung Hee University, Seoul, South Korea e Department of Endocrinology and Metabolism, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea f Department of Obstetrics and Gynecology, Yong-San Hospital, Chung-Ang University, Seoul, South Korea According to recent studies, Korea has been reported to be one of the countries with the lowest serum 25(OH)D levels. However, these studies were mostly based on outpatient subjects. So far as we know, there has been no population-based study on the prevalence of vitamin D inadequacy in Korea. Therefore, we analyzed the prevalence of vitamin D inadequacy in participants of the Chungju Metabolic Disease Cohort Study and associated serum 25(OH)D levels with bone mineral density (BMD) values and results of balance function tests. This study was nested in the Chungju Metabolic Disease Cohort Study which began in 2003, based in the province of Chungju, Korea. Data of 1303 participants who responded in 2007 were analyzed. BMD at the lumbar spine and femur was measured by dual energy Xray absorptiometry (Hologic DQR 4500). Serum 25(OH)D levels were measured with the LIAISON chemiluminescence assay (CLIA, Diasorin). 100 age- and sex-matched subjects were randomly selected and had their serum 25(OH)D levels measured with both the Diasorin CLIA method and the Diasorin RIA (radioimmunoassay) method to

P289 Oral calcitonin protects against cartilage degradation K. Henriksen, M.A. Karsdal⁎ Pharmacology, Nordic Bioscience, Herlev, Denmark Background: Bone resorption displays marked diurnal variation. Completely reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks, i.e. during the night. Aim: The aim of the study was to assess the association between the bioavailability of 0.8 mg of oral salmon calcitonin (sCT) given as a single dose in the morning, pre-dinner, or in the evening and the pharmacodynamic (PD) profiles, and to assess the intra-individual absorption. Methods: Participants were from two randomized, double-blind, placebo-controlled studies. Study I was a cross-over study including healthy postmenopausal women receiving a single dose of 0.8 mg of oral sCT given as a morning dose at 08:00 (n = 42), a pre-dinner dose at 17:00 (n = 20), and an evening dose at 22:00 (n = 19) or placebo. Blood samples were taken before drug intake, and at 5, 10, 15, 30, 45 min, 1, 11/2, 2, 21/2, 3 h, and every hour until 24 h after dosing. Study 2 was a 14-day treatment study including postmenopausal women and men (n = 73) suffering from osteoarthritis (OA). One of the treatment arms comprised administration of 0.8 mg of oral sCT given twice daily with one dose given in the morning at 08:00 and one dose given pre-dinner at 17:00 (n = 26). On treatment day 1 and day 14, blood samples were taken before drug intake, and at 10, 15, 30, 45 min, and 1, 2, and 4 h for plasma sCT measurements. In both studies the absorption of calcitonin was assessed by measurement of plasma sCT concentrations, and bone resorption by the biochemical marker of serum CTX. Results: Overall, dosing with oral sCT resulted in a significant suppression of serum CTX over placebo irrespective of dosing time and level of absorption of sCT. At all three dosing times a significantly higher suppression was observed in subjects with the highest intestinal absorption of sCT. The effect of increased absorption of sCT was a marked prolongation of the suppression whereas the acute suppression 1 to 2 h after dosing was unaffected. The variation in the absorption of sCT did not seem to be inherent with the individual