Skip to main content
Erschienen in: Osteoporosis International 1/2014

01.01.2014 | Original Article

Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures

verfasst von: H. Johansson, A. Odén, E. V. McCloskey, J. A. Kanis

Erschienen in: Osteoporosis International | Ausgabe 1/2014

Einloggen, um Zugang zu erhalten

Abstract

Summary

In this meta-analysis of the control arms of four phase 3 trials, mild vertebral fractures were a significant risk factor for future vertebral fractures but not for non-vertebral fracture.

Introduction

A prior vertebral fracture is a risk factor for future fracture that is commonly used as an eligibility criterion for treatment and in the assessment of fracture probability. The aim of this study was to determine the prognostic significance of a morphometric fracture according to the severity of fracture.

Methods

We examined the control (placebo) treated arms of four phase 3 trials. Vertebral fracture status was graded at baseline in 7,623 women, and fracture outcomes were documented over the subsequent 20,000 patient-years. Fracture outcomes were characterised as a further vertebral fracture, a non-vertebral fracture or a clinical fracture (non-vertebral plus clinical vertebral fracture). The relative risk of fracture was computed from the merged β coefficients of each trial weighted according to the variance.

Results

Mild vertebral fractures were a significant risk factor for vertebral fractures [risk ratio (RR) = 2.17; 95 % CI = 1.70–2.76] but were not associated with an increased risk of non-vertebral fractures (RR = 1.08; 95 % CI = 0.86–1.36). Moderate/severe vertebral fractures were associated with a high risk of vertebral fractures (RR = 4.23; 95 % CI = 3.58–5.00) and a moderate though significant increase in non-vertebral fracture risk (RR = 1.64; 95 % CI = 1.38–1.94).

Conclusions

Prior moderate/severe morphometric vertebral fractures are a strong and significant risk factor for future fracture. The presence of a mild vertebral fracture is of no significant prognostic value for non-vertebral fractures. These findings should temper the use of morphometric fractures in the assessment of risk and the design of phase 3 studies.
Literatur
1.
Zurück zum Zitat Delmas PD, Marin F, Marcus R, Misurski DA, Mitlak BH (2007) Beyond hip: importance of other nonspinal fractures. Am J Med 120:381–7PubMedCrossRef Delmas PD, Marin F, Marcus R, Misurski DA, Mitlak BH (2007) Beyond hip: importance of other nonspinal fractures. Am J Med 120:381–7PubMedCrossRef
2.
Zurück zum Zitat Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Br Med J 312:1254–9CrossRef Marshall D, Johnell O, Wedel H (1996) Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. Br Med J 312:1254–9CrossRef
3.
Zurück zum Zitat Dawson-Hughes B; National Osteoporosis Foundation Guide Committee (2008) A revised clinician's guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab 93:2463–5CrossRef Dawson-Hughes B; National Osteoporosis Foundation Guide Committee (2008) A revised clinician's guide to the prevention and treatment of osteoporosis. J Clin Endocrinol Metab 93:2463–5CrossRef
4.
Zurück zum Zitat Compston J, Cooper A, Cooper C, on behalf of the National Osteoporosis Guideline Group (NOGG) et al (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62:105–108PubMedCrossRef Compston J, Cooper A, Cooper C, on behalf of the National Osteoporosis Guideline Group (NOGG) et al (2009) Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. Maturitas 62:105–108PubMedCrossRef
5.
Zurück zum Zitat Papaioannou A, Morin S, Cheung AM et al (2010) 2010 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182:1864–73PubMedCentralPubMedCrossRef Papaioannou A, Morin S, Cheung AM et al (2010) 2010 Clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182:1864–73PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y on behalf of the Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF) (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57CrossRef Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster J-Y on behalf of the Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF) (2013) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 24:23–57CrossRef
7.
Zurück zum Zitat McCloskey EV, Kanis JA (1996) The assessment of vertebral deformity. In: Genant H, Jergas M, van Kuijk C (eds) Vertebral fracture in osteoporosis. University of California, San Francisco, pp 215–233 McCloskey EV, Kanis JA (1996) The assessment of vertebral deformity. In: Genant H, Jergas M, van Kuijk C (eds) Vertebral fracture in osteoporosis. University of California, San Francisco, pp 215–233
8.
Zurück zum Zitat Jiang G, Eastell R, Barrington NA, Ferrar L (2004) Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis. Osteoporos Int 15:887–96PubMedCrossRef Jiang G, Eastell R, Barrington NA, Ferrar L (2004) Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis. Osteoporos Int 15:887–96PubMedCrossRef
9.
Zurück zum Zitat Black DM, Palermo L, Nevitt MC, Genant HK, Christensen L, Cummings SR (1999) Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 14:90–101PubMedCrossRef Black DM, Palermo L, Nevitt MC, Genant HK, Christensen L, Cummings SR (1999) Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 14:90–101PubMedCrossRef
10.
Zurück zum Zitat Eastell R, Cedel SL, Wahner HW, Riggs BL, Melton LJ (1991) Classification of vertebral fractures. J Bone Miner Res 6:207–15PubMedCrossRef Eastell R, Cedel SL, Wahner HW, Riggs BL, Melton LJ (1991) Classification of vertebral fractures. J Bone Miner Res 6:207–15PubMedCrossRef
11.
Zurück zum Zitat Genant HK, Jergas M, Palermo L et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–96PubMedCrossRef Genant HK, Jergas M, Palermo L et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–96PubMedCrossRef
12.
Zurück zum Zitat Cooper C, Atkinson EJ, O'Fallon WM, Melton LJ 3rd (1992) Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res 7:221–7PubMedCrossRef Cooper C, Atkinson EJ, O'Fallon WM, Melton LJ 3rd (1992) Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985–1989. J Bone Miner Res 7:221–7PubMedCrossRef
13.
Zurück zum Zitat Ettinger B, Black DM, Nevitt MC et al (1992) Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 7:449–56PubMedCrossRef Ettinger B, Black DM, Nevitt MC et al (1992) Contribution of vertebral deformities to chronic back pain and disability. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 7:449–56PubMedCrossRef
14.
Zurück zum Zitat Johnell O, Gullberg B, Kanis JA (1997) The hospital burden of vertebral fracture in Europe: a study of national register sources. Osteoporos Int 7:138–44PubMedCrossRef Johnell O, Gullberg B, Kanis JA (1997) The hospital burden of vertebral fracture in Europe: a study of national register sources. Osteoporos Int 7:138–44PubMedCrossRef
15.
Zurück zum Zitat Van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. Bone 29:517–22PubMedCrossRef Van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001) Epidemiology of fractures in England and Wales. Bone 29:517–22PubMedCrossRef
16.
Zurück zum Zitat Kanis JA, Johnell O, Oden A et al (2004) The risk and burden of vertebral fractures in Sweden. Osteoporos Int 15:20–6PubMedCrossRef Kanis JA, Johnell O, Oden A et al (2004) The risk and burden of vertebral fractures in Sweden. Osteoporos Int 15:20–6PubMedCrossRef
17.
Zurück zum Zitat Lindsay R, Silverman SL, Cooper C et al (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285:320–3PubMedCrossRef Lindsay R, Silverman SL, Cooper C et al (2001) Risk of new vertebral fracture in the year following a fracture. JAMA 285:320–3PubMedCrossRef
18.
Zurück zum Zitat Klotzbuecher CM, Ross PD, Landsman PB, Abbot TA, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–39PubMedCrossRef Klotzbuecher CM, Ross PD, Landsman PB, Abbot TA, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–39PubMedCrossRef
19.
Zurück zum Zitat Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–68PubMedCrossRef Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–68PubMedCrossRef
20.
Zurück zum Zitat Reginster J-Y, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C et al (2005) Strontium ranelate reduces the risk of nonvertebral fracture in postmenopausal women with osteoporosis: TROPOS study. J Clinl Endocrinol Metab 90:2816–22CrossRef Reginster J-Y, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C et al (2005) Strontium ranelate reduces the risk of nonvertebral fracture in postmenopausal women with osteoporosis: TROPOS study. J Clinl Endocrinol Metab 90:2816–22CrossRef
21.
Zurück zum Zitat Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ et al (2008) Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo- and active controlled clinical trial. J Bone Miner Res 23:1923–34PubMedCrossRef Silverman SL, Christiansen C, Genant HK, Vukicevic S, Zanchetta JR, de Villiers TJ et al (2008) Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo- and active controlled clinical trial. J Bone Miner Res 23:1923–34PubMedCrossRef
22.
Zurück zum Zitat Ettinger B, Black DM, Mitlak BH et al. (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282: 637–45. Erratum in: JAMA 1999; 282 :2124. Ettinger B, Black DM, Mitlak BH et al. (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282: 637–45. Erratum in: JAMA 1999; 282 :2124.
23.
Zurück zum Zitat Kanis JA, Johansson H, Oden A, McCloskey EV (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX®. Bone 44:49–54 Kanis JA, Johansson H, Oden A, McCloskey EV (2009) Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX®. Bone 44:49–54
24.
Zurück zum Zitat Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–48PubMedCrossRef Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–48PubMedCrossRef
25.
Zurück zum Zitat Wu CY, Li J, Jergas M, Genant HK (1995) Comparison of semiquantitative and quantitative techniques for the assessment of prevalent and incident vertebral fractures. Osteoporos Int 5:354–70PubMedCrossRef Wu CY, Li J, Jergas M, Genant HK (1995) Comparison of semiquantitative and quantitative techniques for the assessment of prevalent and incident vertebral fractures. Osteoporos Int 5:354–70PubMedCrossRef
26.
Zurück zum Zitat Stone KL, Seeley DG, Lui LY et al (2003) BMD at multiple sites and risk of fracture of multiple types: Long-term results from the study of osteoporotic fractures. J Bone Miner Res 18:1947–54PubMedCrossRef Stone KL, Seeley DG, Lui LY et al (2003) BMD at multiple sites and risk of fracture of multiple types: Long-term results from the study of osteoporotic fractures. J Bone Miner Res 18:1947–54PubMedCrossRef
27.
Zurück zum Zitat Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427PubMedCrossRef Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12:417–427PubMedCrossRef
28.
Zurück zum Zitat Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–486PubMedCrossRef Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–486PubMedCrossRef
29.
Zurück zum Zitat Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward’s triangle. Osteoporos Int 12:438–444PubMedCrossRef Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward’s triangle. Osteoporos Int 12:438–444PubMedCrossRef
30.
Zurück zum Zitat Kanis JA, Jönsson B, Odén A, McCloskey EV (2011) A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®. Osteoporos Int 22:2347–2355, Erratum Osteoporos Int 222357 2358PubMedCrossRef Kanis JA, Jönsson B, Odén A, McCloskey EV (2011) A meta-analysis of the effect of strontium ranelate on the risk of vertebral and non-vertebral fracture in postmenopausal osteoporosis and the interaction with FRAX®. Osteoporos Int 22:2347–2355, Erratum Osteoporos Int 222357 2358PubMedCrossRef
31.
Zurück zum Zitat Kanis JA on behalf of the World Health Organization Scientific Group (2008) Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK. Accessible at http://www.shef.ac.uk/FRAX. Accessed 1 May 2013 Kanis JA on behalf of the World Health Organization Scientific Group (2008) Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Centre, University of Sheffield, UK. Accessible at http://​www.​shef.​ac.​uk/​FRAX. Accessed 1 May 2013
32.
Zurück zum Zitat Kanis JA, Johnell O, De Laet C et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–82PubMedCrossRef Kanis JA, Johnell O, De Laet C et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–82PubMedCrossRef
33.
Zurück zum Zitat Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M (2007) Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int 18:1617–24PubMedCrossRef Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M (2007) Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int 18:1617–24PubMedCrossRef
34.
Zurück zum Zitat Gunnes M, Mellstrom D, Johnell O (1998) How well can a previous fracture indicate a new fracture? A questionnaire study of 29,802 postmenopausal women. Acta Orthop Scand 69:508–512PubMedCrossRef Gunnes M, Mellstrom D, Johnell O (1998) How well can a previous fracture indicate a new fracture? A questionnaire study of 29,802 postmenopausal women. Acta Orthop Scand 69:508–512PubMedCrossRef
35.
Zurück zum Zitat Ross PD, Genant HK, Davis JW, Miller PD, Wasnich RD (1993) Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporos Int 3:120–126PubMedCrossRef Ross PD, Genant HK, Davis JW, Miller PD, Wasnich RD (1993) Predicting vertebral fracture incidence from prevalent fractures and bone density among non-black, osteoporotic women. Osteoporos Int 3:120–126PubMedCrossRef
36.
Zurück zum Zitat Davis JW, Grove JS, Wasnich RD, Ross PD (1999) Spatial relationships between prevalent and incident spine fractures. Bone 24:261–264PubMedCrossRef Davis JW, Grove JS, Wasnich RD, Ross PD (1999) Spatial relationships between prevalent and incident spine fractures. Bone 24:261–264PubMedCrossRef
37.
Zurück zum Zitat Wasnich RD, Davis JW, Ross PD (1994) Spine fracture risk is predicted by non-spine fractures. Osteoporos Int 4:1–5PubMedCrossRef Wasnich RD, Davis JW, Ross PD (1994) Spine fracture risk is predicted by non-spine fractures. Osteoporos Int 4:1–5PubMedCrossRef
38.
Zurück zum Zitat Delmas PD, Genant HK, Crans GG et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRef Delmas PD, Genant HK, Crans GG et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRef
39.
Zurück zum Zitat Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH (2007) Enhanced prediction of fracture risk combining vertebral fracture status and BMD. Osteoporos Int 18:761–70PubMedCrossRef Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH (2007) Enhanced prediction of fracture risk combining vertebral fracture status and BMD. Osteoporos Int 18:761–70PubMedCrossRef
40.
Zurück zum Zitat Black DM, Arden NK, Palermo L, Pearson J, Cummings SR (1999) Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 14:821–828PubMedCrossRef Black DM, Arden NK, Palermo L, Pearson J, Cummings SR (1999) Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group. J Bone Miner Res 14:821–828PubMedCrossRef
41.
Zurück zum Zitat Puisto V, Heliovaara M, Impivaara O et al (2010) Severity of vertebral fracture and risk of hip fracture: a nested case–control study. Osteoporos Int 22:63–68PubMedCrossRef Puisto V, Heliovaara M, Impivaara O et al (2010) Severity of vertebral fracture and risk of hip fracture: a nested case–control study. Osteoporos Int 22:63–68PubMedCrossRef
42.
Zurück zum Zitat Spector TD, McCloskey EV, Doyle DV, Kanis JA (1993) Prevalence of vertebral fracture in women and the relationship with bone density and symptoms: the Chingford Study. J Bone Miner Res 8:817–22PubMedCrossRef Spector TD, McCloskey EV, Doyle DV, Kanis JA (1993) Prevalence of vertebral fracture in women and the relationship with bone density and symptoms: the Chingford Study. J Bone Miner Res 8:817–22PubMedCrossRef
43.
Zurück zum Zitat Pongchaiyakul C, Nguyen ND, Jones G, Center JR, Eisman JA, Nguyen TV (2005) Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J Bone Miner Res 20:1349–55PubMedCrossRef Pongchaiyakul C, Nguyen ND, Jones G, Center JR, Eisman JA, Nguyen TV (2005) Asymptomatic vertebral deformity as a major risk factor for subsequent fractures and mortality: a long-term prospective study. J Bone Miner Res 20:1349–55PubMedCrossRef
44.
Zurück zum Zitat Haentjens P, Johnell O, Kanis JA, Network on Male Osteoporosis in Europe (NEMO) et al (2004) Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men. J Bone Miner Res 19:1933–44PubMedCrossRef Haentjens P, Johnell O, Kanis JA, Network on Male Osteoporosis in Europe (NEMO) et al (2004) Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men. J Bone Miner Res 19:1933–44PubMedCrossRef
Metadaten
Titel
Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures
verfasst von
H. Johansson
A. Odén
E. V. McCloskey
J. A. Kanis
Publikationsdatum
01.01.2014
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 1/2014
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2460-0

Weitere Artikel der Ausgabe 1/2014

Osteoporosis International 1/2014 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.