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Erschienen in: Endocrine 2/2019

04.12.2018 | Original Article

Use of antiosteoporotic drugs and calcium/vitamin D in patients with fragility fractures: impact on re-fracture and mortality risk

verfasst von: Luca Degli Esposti, Anna Girardi, Stefania Saragoni, Stefania Sella, Margherita Andretta, Maurizio Rossini, Sandro Giannini, on the behalf of the Study group

Erschienen in: Endocrine | Ausgabe 2/2019

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Abstract

Purpose

To evaluate the impact of pharmacological treatment in osteoporosis patients with recent fracture and to assess the incidence of subsequent fracture and all-cause mortality.

Methods

This observational retrospective study was based on data from administrative databases of five Italian Local Health Units. Osteoporosis patients aged ≥ 50 years with hospitalization for vertebral or hip fracture occurring between 01/01/2011 and 31/12/2015 were included. Treatment adherence was calculated using the medication possession ratio. Multivariable proportional hazard Cox model was used to identify factors associated with time to re-fracture and all-cause mortality.

Results

A cohort of 3475 patients were included and 41.5% of them did not receive any specific anti-fracture treatment. Among treated patients (N = 2032), the majority (83.6%) received calcium/vitamin D supplementation. Over a mean follow-up of 3 years, the risk of subsequent fractures was 44.4% lower in treated patients compared to untreated ones (HR = 0.556, 95% CI = 0.420–0.735, p < 0.001) and 64.4% lower in those receiving calcium/vitamin D supplementation compared to osteoporosis treatment only (HR = 0.356, 95% CI = 0.237-0.533, p < 0.001). The risk of re-fracture was 77.2% lower in treated patients who were adherent to medication (HR = 0.228, 95% CI = 0.139–0.376, p < 0.001). Treated patients had 64% lower mortality risk over the follow-up compared to untreated ones (HR = 0.360, 95% CI = 0.310–0.418, p < 0.001).

Conclusions

A consistent proportion of osteoporosis patients did not receive specific treatment after a fracture, showing poor adherence to national guidelines on osteoporosis treatment. Osteoporosis drug treatment, and to a greater extent in combination with calcium/vitamin D, and adherence were correlated with lower risk of both re-fracture and all-cause mortality.
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Literatur
1.
Zurück zum Zitat Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646–50. Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993 Jun;94(6):646–50.
3.
Zurück zum Zitat O. Johnell, J.A. Kanis, An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 17(12), 1726–1733 (2006)CrossRefPubMed O. Johnell, J.A. Kanis, An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 17(12), 1726–1733 (2006)CrossRefPubMed
5.
Zurück zum Zitat P. Piscitelli, M. Brandi, H. Cawston, A. Gauthier, J.A. Kanis, J. Compston et al. Epidemiological burden of postmenopausal osteoporosis in Italy from 2010 to 2020: estimations from a disease model. Calcif. Tissue Int. 95(5), 419–427 (2014)CrossRefPubMed P. Piscitelli, M. Brandi, H. Cawston, A. Gauthier, J.A. Kanis, J. Compston et al. Epidemiological burden of postmenopausal osteoporosis in Italy from 2010 to 2020: estimations from a disease model. Calcif. Tissue Int. 95(5), 419–427 (2014)CrossRefPubMed
6.
Zurück zum Zitat M.H. Murad, M.T. Drake, R.J. Mullan, K.F. Mauck, L.M. Stuart, M.A. Lane et al. Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J. Clin. Endocrinol. Metab. 97(6), 1871–1880 (2012)CrossRefPubMed M.H. Murad, M.T. Drake, R.J. Mullan, K.F. Mauck, L.M. Stuart, M.A. Lane et al. Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J. Clin. Endocrinol. Metab. 97(6), 1871–1880 (2012)CrossRefPubMed
7.
Zurück zum Zitat N. Freemantle, C. Cooper, A. Diez-Perez, M. Gitlin, H. Radcliffe, S. Shepherd et al. Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos. Int. 24(1), 209–217 (2013)CrossRefPubMed N. Freemantle, C. Cooper, A. Diez-Perez, M. Gitlin, H. Radcliffe, S. Shepherd et al. Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos. Int. 24(1), 209–217 (2013)CrossRefPubMed
8.
Zurück zum Zitat A. Keshishian, N. Boytsov, R. Burge, K. Krohn, L. Lombard, X. Zhang et al. Examining the treatment gap and risk of subsequent fractures among females with a fragility fracture in the US Medicare population. Osteoporos. Int. 28(8), 2485–2494 (2017)CrossRefPubMedPubMedCentral A. Keshishian, N. Boytsov, R. Burge, K. Krohn, L. Lombard, X. Zhang et al. Examining the treatment gap and risk of subsequent fractures among females with a fragility fracture in the US Medicare population. Osteoporos. Int. 28(8), 2485–2494 (2017)CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat A.A. Yusuf, T.J. Matlon, A. Grauer, R. Barron, D. Chandler, Y. Peng, Utilization of osteoporosis medication after a fragility fracture among elderly Medicare beneficiaries. Arch. Osteoporos. 11(1), 31 (2016)CrossRefPubMed A.A. Yusuf, T.J. Matlon, A. Grauer, R. Barron, D. Chandler, Y. Peng, Utilization of osteoporosis medication after a fragility fracture among elderly Medicare beneficiaries. Arch. Osteoporos. 11(1), 31 (2016)CrossRefPubMed
10.
Zurück zum Zitat J.R. Curtis, A.O. Westfall, H. Cheng, K. Lyles, K.G. Saag, E. Delzell, Benefit of adherence with bisphosphonates depends on age and fracture type: Results from an analysis of 101,038 new bisphosphonate users. J. Bone Miner. Res. 23(9), 1435–1441 (2008)CrossRefPubMedPubMedCentral J.R. Curtis, A.O. Westfall, H. Cheng, K. Lyles, K.G. Saag, E. Delzell, Benefit of adherence with bisphosphonates depends on age and fracture type: Results from an analysis of 101,038 new bisphosphonate users. J. Bone Miner. Res. 23(9), 1435–1441 (2008)CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat M. Hiligsmann, V. Rabenda, H.-J. Gathon, O. Ethgen, J.-Y. Reginster, Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif. Tissue Int. 86(3), 202–210 (2010)CrossRefPubMed M. Hiligsmann, V. Rabenda, H.-J. Gathon, O. Ethgen, J.-Y. Reginster, Potential clinical and economic impact of nonadherence with osteoporosis medications. Calcif. Tissue Int. 86(3), 202–210 (2010)CrossRefPubMed
12.
Zurück zum Zitat L. Tafaro, G. Nati, E. Leoni, R. Baldini, M.S. Cattaruzza, M. Mei et al. Adherence to anti-osteoporotic therapies: role and determinants of ‘spot therapy’. Osteoporos. Int. 24(8), 2319–2323 (2013)CrossRefPubMed L. Tafaro, G. Nati, E. Leoni, R. Baldini, M.S. Cattaruzza, M. Mei et al. Adherence to anti-osteoporotic therapies: role and determinants of ‘spot therapy’. Osteoporos. Int. 24(8), 2319–2323 (2013)CrossRefPubMed
13.
Zurück zum Zitat M. Rossini, G. Bianchi, O. Di Munno, S. Giannini, S. Minisola, L. Sinigaglia et al. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos. Int. 17(6), 914–921 (2006)CrossRefPubMed M. Rossini, G. Bianchi, O. Di Munno, S. Giannini, S. Minisola, L. Sinigaglia et al. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos. Int. 17(6), 914–921 (2006)CrossRefPubMed
14.
Zurück zum Zitat J.A. Kanis, C. Cooper, R. Rizzoli, B. Abrahamsen, N.M. Al-Daghri, M.L. Brandi et al. Identification and management of patients at increased risk of osteoporotic fracture: outcomes of an ESCEO expert consensus meeting. Osteoporos. Int. 28(7), 2023–2034 (2017)CrossRefPubMedPubMedCentral J.A. Kanis, C. Cooper, R. Rizzoli, B. Abrahamsen, N.M. Al-Daghri, M.L. Brandi et al. Identification and management of patients at increased risk of osteoporotic fracture: outcomes of an ESCEO expert consensus meeting. Osteoporos. Int. 28(7), 2023–2034 (2017)CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat D.M. Black, D.E. Thompson, D.C. Bauer, K. Ensrud, T. Musliner, M.C. Hochberg et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J. Clin. Endocrinol. Metab. 85(11), 4118–4124 (2000)CrossRefPubMed D.M. Black, D.E. Thompson, D.C. Bauer, K. Ensrud, T. Musliner, M.C. Hochberg et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J. Clin. Endocrinol. Metab. 85(11), 4118–4124 (2000)CrossRefPubMed
16.
Zurück zum Zitat H.K. Genant, E. Siris, G.G. Crans, D. Desaiah, J.H. Krege, Reduction in vertebral fracture risk in teriparatide-treated postmenopausal women as assessed by spinal deformity index. Bone 37(2), 170–174 (2005)CrossRefPubMed H.K. Genant, E. Siris, G.G. Crans, D. Desaiah, J.H. Krege, Reduction in vertebral fracture risk in teriparatide-treated postmenopausal women as assessed by spinal deformity index. Bone 37(2), 170–174 (2005)CrossRefPubMed
17.
Zurück zum Zitat J. Reginster, H.W. Minne, O.H. Sorensen, M. Hooper, C. Roux, M.L. Brandi et al Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos. Int. 11(1), 83–91 (2000)CrossRefPubMed J. Reginster, H.W. Minne, O.H. Sorensen, M. Hooper, C. Roux, M.L. Brandi et al Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos. Int. 11(1), 83–91 (2000)CrossRefPubMed
18.
Zurück zum Zitat S.R. Cummings, J. San Martin, M.R. McClung, E.S. Siris, R. Eastell, I.R. Reid et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 361(8), 756–765 (2009)CrossRefPubMed S.R. Cummings, J. San Martin, M.R. McClung, E.S. Siris, R. Eastell, I.R. Reid et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med. 361(8), 756–765 (2009)CrossRefPubMed
19.
Zurück zum Zitat P. Ebeling, R. Adler, G. Jones, Management of endocrine disease: Therapeutics of Vitamin D. Eur. J. Endocrinol. 5(179), R239–59 (2018)CrossRef P. Ebeling, R. Adler, G. Jones, Management of endocrine disease: Therapeutics of Vitamin D. Eur. J. Endocrinol. 5(179), R239–59 (2018)CrossRef
22.
Zurück zum Zitat S. Adami, S. Giannini, G. Bianchi, L. Sinigaglia, O. Di Munno, C.E. Fiore et al. Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos. Int. 20(2), 239–244 (2009)CrossRefPubMed S. Adami, S. Giannini, G. Bianchi, L. Sinigaglia, O. Di Munno, C.E. Fiore et al. Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos. Int. 20(2), 239–244 (2009)CrossRefPubMed
23.
Zurück zum Zitat S. Adami, E. Romagnoli, V. Carnevale, A. Scillitani, A. Giusti, M. Rossini et al. [Guidelines on prevention and treatment of vitamin D deficiency. Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)]. Reumatismo 63(3), 129–147 (2011)CrossRef S. Adami, E. Romagnoli, V. Carnevale, A. Scillitani, A. Giusti, M. Rossini et al. [Guidelines on prevention and treatment of vitamin D deficiency. Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)]. Reumatismo 63(3), 129–147 (2011)CrossRef
25.
Zurück zum Zitat M.E. Charlson, P. Pompei, K.L. Ales, C.R. MacKenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40(5), 373–383 (1987)CrossRefPubMed M.E. Charlson, P. Pompei, K.L. Ales, C.R. MacKenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J. Chronic Dis. 40(5), 373–383 (1987)CrossRefPubMed
26.
Zurück zum Zitat C. Cipriani, J. Pepe, F. Bertoldo, G. Bianchi, F.P. Cantatore, A. Corrado et al. The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study. J. Endocrinol. Invest. 41(4), 431–438 (2018)CrossRefPubMed C. Cipriani, J. Pepe, F. Bertoldo, G. Bianchi, F.P. Cantatore, A. Corrado et al. The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study. J. Endocrinol. Invest. 41(4), 431–438 (2018)CrossRefPubMed
27.
Zurück zum Zitat R. Halpern, L. Becker, S.U. Iqbal, L.E. Kazis, D. Macarios, E. Badamgarav, The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitalizations: a retrospective claims analysis of female health plan enrollees with osteoporosis. J. Manag. Care Pharm. 17(1), 25–39 (2011)PubMed R. Halpern, L. Becker, S.U. Iqbal, L.E. Kazis, D. Macarios, E. Badamgarav, The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitalizations: a retrospective claims analysis of female health plan enrollees with osteoporosis. J. Manag. Care Pharm. 17(1), 25–39 (2011)PubMed
29.
Zurück zum Zitat G. Mazziotti, E. Canalis, A. Giustina, Drug-induced osteoporosis: mechanisms and clinical implications. Am. J. Med. 10(123), 877–884 (2010)CrossRef G. Mazziotti, E. Canalis, A. Giustina, Drug-induced osteoporosis: mechanisms and clinical implications. Am. J. Med. 10(123), 877–884 (2010)CrossRef
30.
Zurück zum Zitat G. Mazziotti, A. Formenti, R. Adler, Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine 3(54), 603–611 (2016)CrossRef G. Mazziotti, A. Formenti, R. Adler, Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine 3(54), 603–611 (2016)CrossRef
31.
Zurück zum Zitat P. Vestergaard, L. Rejnmark, L. Mosekilde, Fracture risk associated with different types of oral corticosteroids and effect of termination of corticosteroids on the risk of fractures. PubMed-Ncbi. 4(82), 249–257 (2008) P. Vestergaard, L. Rejnmark, L. Mosekilde, Fracture risk associated with different types of oral corticosteroids and effect of termination of corticosteroids on the risk of fractures. PubMed-Ncbi. 4(82), 249–257 (2008)
32.
Zurück zum Zitat F.-M. Su, Y.-C. Chen, T.-T. Cheng, W.-C. Lin, C.-C. Lui, Is raloxifene associated with lower risk of mortality in postmenopausal women with vertebral fractures after vertebroplasty?: a hospital-based analysis. BMC Musculoskelet. Disord. 16, 209 (2015)CrossRefPubMedPubMedCentral F.-M. Su, Y.-C. Chen, T.-T. Cheng, W.-C. Lin, C.-C. Lui, Is raloxifene associated with lower risk of mortality in postmenopausal women with vertebral fractures after vertebroplasty?: a hospital-based analysis. BMC Musculoskelet. Disord. 16, 209 (2015)CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat M.J. Bolland, A.B. Grey, G.D. Gamble, I.R. Reid, Effect of osteoporosis treatment on mortality: a meta-analysis. J. Clin. Endocrinol. Metab. 95(3), 1174–1181 (2010)CrossRefPubMed M.J. Bolland, A.B. Grey, G.D. Gamble, I.R. Reid, Effect of osteoporosis treatment on mortality: a meta-analysis. J. Clin. Endocrinol. Metab. 95(3), 1174–1181 (2010)CrossRefPubMed
34.
Zurück zum Zitat J.R. Center, T.V. Nguyen, D. Schneider, P.N. Sambrook, J.A. Eisman, Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353(9156), 878–882 (1999)CrossRefPubMed J.R. Center, T.V. Nguyen, D. Schneider, P.N. Sambrook, J.A. Eisman, Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353(9156), 878–882 (1999)CrossRefPubMed
35.
Zurück zum Zitat S. Frara, M. Losa, M. Doga, A.M. Formenti, P. Mortini, G. Mazziotti et al. High prevalence of radiological vertebral fractures in patients with TSH-secreting pituitary adenoma. J. Endocr. Soc. 2(9), 1089–1099 (2018)CrossRefPubMedPubMedCentral S. Frara, M. Losa, M. Doga, A.M. Formenti, P. Mortini, G. Mazziotti et al. High prevalence of radiological vertebral fractures in patients with TSH-secreting pituitary adenoma. J. Endocr. Soc. 2(9), 1089–1099 (2018)CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat G. Mazziotti, A.M. Formenti, S. Frara, R. Olivetti, G. Banfi, M. Memo et al. High prevalence of radiological vertebral fractures in women on thyroid-stimulating hormone-suppressive therapy for thyroid carcinoma. J. Clin. Endocrinol. Metab. 103(3), 956–964 (2018)CrossRefPubMed G. Mazziotti, A.M. Formenti, S. Frara, R. Olivetti, G. Banfi, M. Memo et al. High prevalence of radiological vertebral fractures in women on thyroid-stimulating hormone-suppressive therapy for thyroid carcinoma. J. Clin. Endocrinol. Metab. 103(3), 956–964 (2018)CrossRefPubMed
Metadaten
Titel
Use of antiosteoporotic drugs and calcium/vitamin D in patients with fragility fractures: impact on re-fracture and mortality risk
verfasst von
Luca Degli Esposti
Anna Girardi
Stefania Saragoni
Stefania Sella
Margherita Andretta
Maurizio Rossini
Sandro Giannini
on the behalf of the Study group
Publikationsdatum
04.12.2018
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2019
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-018-1824-9

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