TY - JOUR A1 - Seefried, L. A1 - Rak, D. A1 - Petryk, A. A1 - Genest, F. T1 - Bone turnover and mineral metabolism in adult patients with hypophosphatasia treated with asfotase alfa JF - Osteoporosis International N2 - Summary There is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone. Introduction Hypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP. Methods ALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment. Results Data from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment. Conclusion Significant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care. KW - bone mineral density KW - bone turnover KW - hypophosphatasia KW - enzyme replacement therapy KW - alkaline phosphatase Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265310 VL - 32 IS - 12 ER - TY - JOUR A1 - Genest, F. A1 - Claußen, L. A1 - Rak, D. A1 - Seefried, L. T1 - Bone mineral density and fracture risk in adult patients with hypophosphatasia JF - Osteoporosis International N2 - Summary In adult hypophosphatasia (HPP) patients, elevated lumbar spine dual X-ray absorptiometry (DXA) values are associated with markers of disease severity and disease-specific fracture risk while femoral bone mineral density (BMD), being largely unaffected by the disease severity, may still be useful to monitor other causes of increased fracture risk due to low BMD. Introduction Hypophosphatasia (HPP) is a rare inherited metabolic disorder due to deficient activity of the tissue-nonspecific alkaline phosphatase (TNAP). Clinical manifestation in adult HPP patients is manifold including an increased risk for fractures, but data regarding clinical significance of DXA measurement and associations with fracture risk and disease severity is scarce. Methods Retrospective single-center analysis of DXA scans in patients with confirmed HPP (documented mutation, clinical symptoms, low alkaline phosphatase activity). Further data evaluation included disease-related fractures, laboratory results (alkaline phosphatase, pyridoxalphosphate, phosphoethanolamine), and medical history. Results Analysis included 110 patients (84 female, mean age of 46.2 years) of whom 37.3% (n = 41) were harboring two mutations. Average T-Score level at the lumbar spine was − 0.1 (SD 1.9), and mean total hip T-Score was − 1.07 (SD 0.15). Both lower ALP activity and higher substrate levels (pyridoxalphosphate and phosphoethanolamine) were significantly correlated with increased lumbar spine T-Score levels (p < 0.001) while BMD at the hip was not affected by indicators of disease severity. Increased lumbar spine BMD was significantly associated with an increased risk for HPP-related fractures, prevalent in 22 (20%) patients (p < 0.001) with 21 of them having biallelic mutations. Conclusion BMD in adult HPP patients is not systematically reduced. Conversely, increased lumbar spine BMD appears to be associated with severely compromised mineralization and increased risk for HPP-related fractures while BMD at the hip appears unaffected by indicators of disease severity, suggesting suitability of this anatomic location for assessing and discerning disorders with increased fracture risk owing to reduced BMD like osteoporosis. Trial registration number German register for clinical studies (DRKS00014022) Date of registration 02/10/2018 – retrospectively registered KW - bone mineral density KW - fracture risk KW - hypophosphatasia KW - osteoporosis KW - pseudofracture Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235793 SN - 0937-941X VL - 32 ER - TY - JOUR A1 - Kemmler, Wolfgang A1 - Kohl, Matthias A1 - Jakob, Franz A1 - Engelke, Klaus A1 - Stengel, Simon von T1 - Effects of high intensity dynamic resistance exercise and whey protein supplements on osteosarcopenia in older men with low bone and muscle mass. Final results of the randomized controlled FrOST study JF - Nutrients N2 - The present study aimed to evaluate the effect of high intensity dynamic resistance exercise (HIT-DRT) and whey protein supplementation (WPS) on bone mineral density (BMD) and sarcopenia parameters in osteosarcopenic men. Men ≥ 72 years with osteosarcopenia (n = 43) were randomly assigned to a HIT-RT (HIT-RT: n = 21) or a non-training control group (n = 22). Supervised HIT-RT twice/week was applied for 18 months, while the control group maintained their habitual lifestyle. Supplying WPS, total protein intake amounted to 1.5–1.6 (HIT-RT) and 1.2 g/kg/body mass/d (control). Both groups were supplied with calcium and vitamin D. Primary study outcomes were BMD and the sarcopenia Z-score. After adjusting for multiplicity, we observed significant positive effects for sarcopenia Z-score (standardized mean difference (SMD): 1.40), BMD at lumbar spine (SMD: 0.72) and total hip (SMD: 0.72). In detail, effect sizes for skeletal muscle mass changes were very pronounced (1.97, p < 0.001), while effects for functional sarcopenia parameters were moderate (0.87, p = 0.008; handgrip strength) or low (0.39, p = 0.209; gait velocity). Apart from one man who reported short periods of temporary worsening of existing joint pain, no HIT-RT/WPS-related adverse effects or injuries were reported. We consider HIT-RT supported by whey protein supplementation as a feasible, attractive, safe and highly effective option to fight osteosarcopenia in older men. KW - resistance exercise KW - osteopenia KW - sarcopenia KW - bone mineral density Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211108 SN - 2072-6643 VL - 12 IS - 8 ER - TY - JOUR A1 - Grote, Stefan A1 - Noeldeke, Tatjana A1 - Blauth, Michael A1 - Mutschler, Wolf A1 - Bürklein, Dominik T1 - Mechanical torque measurement in the proximal femur correlates to failure load and bone mineral density ex vivo JF - Orthopedic Reviews (Pavia) N2 - Knowledge of local bone quality is essential for surgeons to determine operation techniques. A device for intraoperative measurement of local bone quality has been developed by the AO-Research Foundation (DensiProbe®). We used this device to experimentally measure peak breakaway torque of trabecular bone in the proximal femur and correlated this with local bone mineral density (BMD) and failure load. Bone mineral density of 160 cadaver femurs was measured by ex situ dual-energy X-ray absorptiometry. The failure load of all femurs was analyzed by side-impact analysis. Femur fractures were fixed and mechanical peak torque was measured with the DensiProbe® device. Correlation was calculated whereas correlation coefficient and significance was calculated by Fisher’s Z-transformation. Moreover, linear regression analysis was carried out. The unpaired Student’s t-test was used to assess the significance of differences. The Ward triangle region had the lowest BMD with 0.511 g/cm2 (±0.17 g/cm2), followed by the upper neck region with 0.546 g/cm2 (±0.16 g/cm2), trochanteric region with 0.685 g/cm2 (±0.19 g/cm2) and the femoral neck with 0.813 g/cm2 (±0.2 g/cm2). Peak torque of DensiProbe® in the femoral head was 3.48 Nm (±2.34 Nm). Load to failure was 4050.2 N (±1586.7 N). The highest correlation of peak torque measured by Densi Probe® and load to failure was found in the femoral neck (r=0.64, P<0.001). The overall correlation of mechanical peak torque with T-score was r=0.60 (P<0.001). A correlation was found between mechanical peak torque, load to failure of bone and BMD in vitro. Trabecular strength of bone and bone mineral density are different aspects of bone strength, but a correlation was found between them. Mechanical peak torque as measured may contribute additional information about bone strength, especially in the perioperative testing. KW - hip fracture KW - bone mineral density KW - osteoporosis KW - mechanical torque measurement KW - failure load Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132358 VL - 5 IS - e16 ER - TY - JOUR A1 - Haring, Bernhard A1 - Pettinger, Mary A1 - Bea, Jennifer W. A1 - Wactawski-Wende, Jean A1 - Carnahan, Ryan M. A1 - Ockene, Judith K. A1 - Wyler von Ballmoos, Moritz A1 - Wallace, Robert B. A1 - Wassertheil-Smoller, Sylvia T1 - Laxative use and incident falls, fractures and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative JF - BMC Geriatrics N2 - Background Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density [BMD] have not previously been investigated. Methods This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (≥2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI. Results Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95% confidence interval [CI], 1.03-1.10) for falls, 1.02 (95% CI, 0.85-1.22) for hip fractures and 1.01 (95% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake. Conclusion These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use. KW - laxative KW - use KW - fall KW - fracture KW - bone mineral density KW - aging Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95960 UR - http://www.biomedcentral.com/1471-2318/13/38 ER -