@phdthesis{Emmert2002,
  author    = {Emmert, Andrea},
  title     = {Die Knochendichte am proximalen Femur bei gesunden Deutschen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-3955},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {Die Knochendichte ist ein Maß f{\"u}r die Bruchfestigkeit eines Knochens. Ihre Erfassung spielt eine wichtige Rolle in Pr{\"a}vention und Diagnostik der Osteoporose. Um die gemessenen Knochendichtewerte eines Patienten beurteilen zu k{\"o}nnen, sind Referenzwerte notwendig, die das Geschlecht, das Alter und bei den Frauen den Menopausenstatus mitber{\"u}cksichtigen. Da geographisch bedingte Unterschiede in der Knochendichte bestehen, ist es sinnvoll Referenzdaten aus dem Gebiet zu rekrutieren, f{\"u}r das sie sp{\"a}ter auch gelten sollen. In der vorliegenden Studie wurde die Knochendichte an 3 Lokalisationen des proximalen Femur gemessen, am Schenkelhals, am Trochanter und am Ward´s Triangle. Das Kollektiv bestand aus 695 gesunden deutschen M{\"a}nnern und Frauen zwischen 18 und 80 Jahren, mit einer Gewichtung im mittleren Altersbereich. Anhand eines Fragebogens wurden das Alter, die K{\"o}rpermaße und die wichtigsten anamnestischen Daten erfasst und nach Anwendung von Ausschlußkriterien nur gesunde, weder medikament{\"o}s, noch famili{\"a}r belastete Probanden in die Auswertungen miteinbezogen. Die Probanden stammen aus 3 deutschen St{\"a}dten, aus Halle, Chemnitz und K{\"o}ln. Die Knochendichtemessungen wurden durch einen DXA Osteodensitometer (QDR 1000, Hologic) vorgenommen, der in einem Meßfahrzeug installiert war. Somit war der Einsatz desselben Osteodensitometers an verschiedenen Orten m{\"o}glich und das Zusammenf{\"u}gen der gemessenen Daten unproblematisch. Bei einem Teil des Kollektivs wurden Griffst{\"a}rkemessungen durchgef{\"u}hrt. Die Probanden wurden getrenntgeschlechtlich in Dekaden unterteilt und f{\"u}r jede Altersgruppe die durchschnittliche Knochendichte mit Standardabweichung dargestellt. F{\"u}r die Knochendichte am Schenkelhals und am Ward´s triangle wurden zus{\"a}tzlich die Spannweiten zwischen plus/minus 1 Standardabweichung und plus/minus 2 Standardabweichungen ermittelt und tabellarisch aufgelistet. Untersucht wurde der Einfluß von Alter, Gr{\"o}ße, Gewicht, bei einem Teilkollektiv der Griffst{\"a}rke und bei den Frauen des Menopausenstatus auf die Knochendichte. Die Untersuchung f{\"u}hrte zu folgenden Ergebnissen: - Die Analyse {\"u}ber den Altersgang der Knochendichte zeigt eine - mit zunehmendem Alter einhergehende - Abnahme der Konochendichte, insbesondere bei den Frauen. Stark betroffen ist dabei die Knochendichte am Ward´s Triangle, etwas geringer betroffen die Knochendichte am Schenkelhals. - Das K{\"o}rpergewicht hat eine deutliche und beg{\"u}nstigende Wirkung auf die Knochendichte am proximalen Femur bei M{\"a}nnern und Frauen, insbesondere auf den Schenkelhals. Dieser Einfluß {\"u}bertrifft in unserem, eher j{\"u}ngeren Kollektiv auch die altersbedingte Wirkung an der Knochendichte. - Die Griffst{\"a}rke repr{\"a}sentiert die Muskelkraft, die bei den M{\"a}nnern und pr{\"a}menopausalen Frauen eine positive und signifikante Korrelation zur Knochendichte zeigt. - Die K{\"o}rpergr{\"o}ße hat verglichen mit den anderen anthropometrischen Werten eine geringe Auswirkung auf die Knochendichte am proximalen Femur. - Der Menopausenstatus beeinflußt die altersabh{\"a}ngigen Ver{\"a}nderungen an der Knochendichte, v.a. am Ward´s Triangle. So ist bei den postmenopausalen Frauen der j{\"a}hrliche Knochendichteverlust h{\"o}her, als bei den Frauen vor der Menopause. - Wir fanden keine relevanten Unterschiede zwischen unseren Knochendichtewerten und den Werten von weißen US-Amerikanern aus einer anderen Studie. Das l{\"a}ßt auf eine Vergleichbarkeit von deutschen und nordamerikanischen Knochendichtewerten schließen.},
  language  = {de}
}
@article{GenestClaussenRaketal.2021,
  author    = {Genest, F. and Claußen, L. and Rak, D. and Seefried, L.},
  title     = {Bone mineral density and fracture risk in adult patients with hypophosphatasia},
  series = {Osteoporosis International},
  volume    = {32},
  journal   = {Osteoporosis International},
  issn      = {0937-941X},
  doi       = {10.1007/s00198-020-05612-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235793},
  pages     = {377-385},
  year      = {2021},
  abstract  = {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},
  language  = {en}
}
@article{GroteNoeldekeBlauthetal.2013,
  author    = {Grote, Stefan and Noeldeke, Tatjana and Blauth, Michael and Mutschler, Wolf and B{\"u}rklein, Dominik},
  title     = {Mechanical torque measurement in the proximal femur correlates to failure load and bone mineral density ex vivo},
  series = {Orthopedic Reviews (Pavia)},
  volume    = {5},
  journal   = {Orthopedic Reviews (Pavia)},
  number    = {e16},
  doi       = {10.4081/or.2013.e16},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132358},
  year      = {2013},
  abstract  = {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.},
  language  = {en}
}
@article{HaringPettingerBeaetal.2013,
  author    = {Haring, Bernhard and Pettinger, Mary and Bea, Jennifer W. and Wactawski-Wende, Jean and Carnahan, Ryan M. and Ockene, Judith K. and Wyler von Ballmoos, Moritz and Wallace, Robert B. and Wassertheil-Smoller, Sylvia},
  title     = {Laxative use and incident falls, fractures and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative},
  series = {BMC Geriatrics},
  journal   = {BMC Geriatrics},
  doi       = {10.1186/1471-2318-13-38},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-95960},
  year      = {2013},
  abstract  = {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.},
  language  = {en}
}
@article{KemmlerKohlJakobetal.2020,
  author    = {Kemmler, Wolfgang and Kohl, Matthias and Jakob, Franz and Engelke, Klaus and Stengel, Simon von},
  title     = {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},
  series = {Nutrients},
  volume    = {12},
  journal   = {Nutrients},
  number    = {8},
  issn      = {2072-6643},
  doi       = {10.3390/nu12082341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211108},
  year      = {2020},
  abstract  = {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.},
  language  = {en}
}
@phdthesis{Schneider2012,
  author    = {Schneider, Mara},
  title     = {Effects of levothyroxine on bone mineral density, muscle force and bone turnover markers: A cohort study},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85173},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {The objective of this prospective observational controlled study was to evaluate potential effects and dose-response relationship of LT4 administration on BMD, parameters of bone and muscle strength, and biochemical variables of calcium homoeostasis and bone turnover.Ninety-seven men and pre-menopausal women after near total thyroidectomy and ¹³¹I remnant ablation for well-differentiated thyroid carcinoma or after strumectomy for non-toxic goitre were stratified by degree of TSH suppression and by gender in three subgroups: 28 men and 46 women on LT4 suppressive treatment and 23 women on LT4 replacement therapy. Patients were matched for age, gender and BMI to 89 healthy controls with a negative history of thyroid disease. Patients and controls were followed and studied for a mean time of 1.1±0.2 years. Peripheral volumetric total and trabecular BMD as well as bone strength (pQCT) were determined at the ultra-distal radius. Central areal BMD (DXA) was measured at the lumbar spine, left and right femoral neck as well as left and right total hip. Maximum grip strength (dynamometer) of the non-dominant forearm and serum markers of calcium and bone metabolism were assessed. BMD at the axial skeleton and muscle strength were not impaired by LT4 medication irrespective of gender, underlying diagnosis or treatment regimen. By contrast, a general trend of inversely affected total and trabecular BMD and of decreased bone strength was detected at the ultra-distal radius. Only in women on LT4 suppressive treatment, loss of total BMD at the ultra-distal radius reached a level of high significance. In women on LT4 replacement therapy, a significant decline of maximum grip strength appeared in comparison with female controls, while appendicular total and trabecular BMD as well as bone strength remained unchanged and did not differ from respective controls. In men on LT4 suppressive treatment, greater reduction of bone strength as compared to female thyroid cancer patients was marginally significant. Calcium balance was stable and serum concentrations of bone metabolism markers levelled off or rather decreased contradicting (high turnover) bone loss. The study did not reveal any dose-related differential influence of LT4 administration either on primary or secondary study endpoints in female patients. A gender-related difference of bone strength in response to LT4 suppressive treatment might not be excluded, as male thyroid cancer patients showed greater decline of bone strength despite unaffected peripheral BMD and muscle strength. In conclusion, there was only little evidence of adverse LT4 effects. For the most part, LT4 administration irrespective of degree of TSH suppression was not associated with low or accelerated loss of BMD at the peripheral and central skeleton and loss of bone and muscle strength, a finding also confirmed biochemically. The ultra-distal radius as a non-weight bearing skeletal site might be at risk for BMD reduction. According to the results, pre-menopausal women on LT4 suppressive therapy might be at risk of bone loss. The more complex approach of this study also took into account biomechanical qualities of bone material as well as structural and geometrical characteristics of bone architecture implying a causal muscle-bone interrelationship.},
  subject      = {Schilddr{\"u}se},
  language  = {en}
}
@article{SeefriedRakPetryketal.2021,
  author    = {Seefried, L. and Rak, D. and Petryk, A. and Genest, F.},
  title     = {Bone turnover and mineral metabolism in adult patients with hypophosphatasia treated with asfotase alfa},
  series = {Osteoporosis International},
  volume    = {32},
  journal   = {Osteoporosis International},
  number    = {12},
  doi       = {10.1007/s00198-021-06025-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265310},
  pages     = {2505-2513},
  year      = {2021},
  abstract  = {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.},
  language  = {en}
}