Ariane Leboime

Osteoporosis and mortality

Osteoporosis is classified as a public health problem by healthcare authorities because it is associated with an increased risk of potentially serious fractures. Osteoporotic fractures are known to generate a heavy burden of morbidity and financial cost [1]. However, recent data indicate that some osteoporotic fractures are also associated with excess mortality. These data have led to public health measures such as the addition by the World Health Organization of fracture prevention to the list of public health priorities [2] and the update on hip fractures issued recently by the statistics department of the French ministry of health (DREES [3]). Hip fractures constitute the most severe complication of osteoporosis because they can induce permanent physical disability, loss of self-sufficiency, institutionalization and, above all, an increased risk of death. Interestingly, two recent publications support the hypothesis that optimal osteoporosis management may affect the risk of death. Here, we will review the main data linking osteoporotic fractures overall (as opposed to hip fractures only) and mortality.

Severity of osteoporosis: what is the impact of co-morbidities?

The co-morbidity profile varies widely across postmenopausal women with osteoporosis, and comorbidities often adversely affect the management of osteoporosis. There is a need for detailed information on the co-morbidities that may affect the course of osteoporosis by increasing the risk of subsequent fractures or inducing multiple fractures. We consequently reviewed the literature on the most common co-morbidities in adults older than 50 years of age, with special attention to published meta-analyses. We found that osteoporosis severity was increased not only by conventional risk factors, but also by a number of conditions including inflammatory bowel and joint diseases with or without glucocorticoid therapy, breast cancer and prostate cancer treated with chemotherapy or hormone therapy, diabetes (chiefly type 1), and celiac disease. Studies suggest an adverse impact of moderate renal failure and depression, although their methodological weaknesses preclude definitive conclusions. In practice, these co-morbidities should be taken into account when evaluating the fracture risk and making treatment decisions.

Severe osteoporosis: diagnosis and follow-up. Lessons for clinical practice

The management of osteoporosis has improved considerably, leading to the development of new goals. A major concern today is the management of patients with severe osteoporosis, in whom the need for pharmacotherapy is clear [1]. Epidemiological data have established that osteoporosis is associated with severe complications [2,3]. Furthermore, osteoporosis is now recognized as a complication of several chronic diseases, whose presence adversely affects the management of osteoporosis. The ODISSEE task force (Osteoporosis DIagnosis and Surveillance of SEvErity) was established to answer practical questions regarding the management of severe osteoporosis, based on evidence in the literature. Several groups conducted an exhaustive literature review, and advice was obtained from a panel of French rheumatologists. The ODISSEE scientific committee then developed the first consensus statement on the diagnosis, follow-up and management of severe osteoporosis. This statement was validated by a panel of 70 French rheumatologists at the first national ODISSEE meeting held on November 13-14, 2009.

Stabilized severe osteoporosis: should the treatment be stopped?

Several medications have been proven to decrease the risk of postmenopausal osteoporotic fractures of the spine, hip, or peripheral skeleton. However, the optimal duration of treatment with these medications has not been determined. The efficacy data come chiefly from controlled trials conducted over 3 to 5 years in elderly women at high risk for fractures. Some of these trials were followed by open-label extension phases that showed sustained bone mineral density gains over 7 to 10 years. The data pointing to a sustained decrease in the fracture rate beyond 4-5 years of treatment vary across studies and drugs but are generally scant and open to criticism. The published evidence does not suggest a need for stopping osteoporosis medications after the first 4-5 years out of concern about bisphosphonate-induced osteonecrosis of the jaw or alendronate-induced atypical fractures. Given that pharmacotherapy targets patients with severe osteoporosis, continued treatment beyond the first 5 years is probably warranted in most cases.

Defining treatment failure in severe osteoporosis

The management of postmenopausal osteoporosis has benefited from the recent introduction of several new drug classes and is now well standardized. However, none of the available osteoporosis drugs completely abolishes the occurrence of fractures. Therefore, criteria are needed to determine when the occurrence of a fracture during treatment indicates failure to respond to the drug. Such criteria would improve patient management. A panel of national osteoporosis experts was convened to discuss data from a literature review on severe osteoporosis (Osteoporosis DIagnosis and Surveillance of SEvErity, ODISSEE). The experts reached a consensus that an inadequate response to treatment for postmenopausal osteoporosis is the occurrence, in a patient with severe osteoporosis, adequate calcium and vitamin D intakes, and good treatment adherence, of any of the following: incident major fracture within the first treatment year, more than one minor insufficiency fracture, or a bone mineral density decrease by at least the smallest significant amount (0.03 g/cm(2)) after 5 years or earlier in the event of a minor fracture.

Management of patients with incident fractures during osteoporosis treatment.

Official recommendations are available for detecting osteoporosis and initiating osteoporosis medications in postmenopausal women. However, there are no recommendations about the management of patients with incident fractures despite osteoporosis therapy. Second-line osteoporosis treatments have been evaluated only based on laboratory and absorptiometry criteria. Nevertheless, we will try to answer the following questions: (1) What criteria should be used to determine whether a fracture during osteoporosis treatment indicates treatment failure (low-energy fracture, fracture not due to an intercurrent health condition, fracture of the type targeted by the osteoporosis treatment, sufficient treatment duration at occurrence of the fracture, and good adherence to the treatment and to vitamin D supplementation)? (2) In patients with treatment failure or an inadequate clinical response, defined as a fracture despite adherence to osteoporosis therapy for at least 1 year, what are the best treatment strategies?

Severe osteoporosis: does structural monitoring help?

Vertebral fractures, the most common osteoporotic fractures, are associated with excess mortality even in the absence of symptoms. Presence of at least one radiological or clinical prevalent vertebral fracture increases the risk of incident vertebral fractures not only in untreated patients, but also in treated patients, as established by studies involving routine radiological monitoring. Therefore, whether structural monitoring is indicated on a routine basis deserves discussion. Height measurement is a basic monitoring tool for detecting new vertebral fractures. However, loss of height is nonspecific. Radiography involves radiation exposure levels and financial costs that are not consistent with use for routine monitoring. Vertebral fracture assessment based on dual-energy X-ray absorptiometry (VFA), in contrast, is an inexpensive method that delivers only low radiation levels. VFA used in conjunction with absorptiometry may be well suited to the monitoring of women with severe osteoporosis.

Ostéoporose et mortalité

Resume L’osteoporose est consideree comme un probleme de sante publique par les autorites de sante en raison de la gravite potentielle de certaines fractures dont elle augmente le risque. La morbidite et le cout de ces fractures sont bien connus, mais des donnees recentes soulignent l’impact de certaines fractures sur la mortalite. Ce lien a justifie par exemple la mise au point recente de la DREES (Direction de la recherche des etudes de l’evaluation et des statistiques du ministere de la Sante) a propos des fractures de l’extremite superieure du femur (ESF) [1]. Cette fracture est la complication la plus grave de l’osteoporose, en raison de l’incapacite physique permanente residuelle dont elle peut etre la cause, de la perte d’independance, de l’institutionnalisation, et surtout d’une augmentation du risque de mortalite. Au-dela de la fracture de l’ESF, d’autres fractures sont associees a une surmortalite. De maniere interessante, deux publications recentes soulignent l’hypothese qu’une prise en charge therapeutique optimale des patients osteoporotiques pourrait influer sur ce risque. Nous nous proposons de revoir ici les principales donnees associant les fractures osteoporotiques (au-dela de la fracture de l’ESF) et la mortalite.

Faut-il interrompre le traitement d'une ostéoporose sévère qui est stabilisée ?

Resume Plusieurs traitements ont demontre leur capacite a reduire le risque de fractures chez les femmes menopausees osteoporotiques que ce soit pour les fractures vertebrales, les fractures de hanche ou les fractures peripheriques. La duree optimale d’utilisation de ces traitements n’est pas etablie. Ces traitements ont essentiellement fait la preuve de leur efficacite dans des etudes controlees de trois a cinq ans, chez des femmes âgees, a haut risque fracturaire. Certains d’entre eux ont beneficie d’extension en ouvert allant jusque 7 a 10 ans de suivi avec la persistance de l’efficacite de ces traitements sur le gain de densite minerale osseuse. Les preuves d’une efficacite antifracturaire au-dela de 4-5 ans sont variables selon les etudes et les molecules, mais il y a peu d’etudes et elles sont critiquables pour la plupart. Le risque d’osteonecrose de machoire sous bisphosphonates et la survenue de fractures atypiques sous alendronate ne justifient pas, au regard des donnees de la litterature, d’interrompre un traitement anti-osteoporotique apres une premiere sequence therapeutique de 4 a 5 ans. Par consequent, la poursuite des traitements doit alors prendre en compte l’evaluation initiale du risque de fracture et son evolution apres une premiere sequence therapeutique de 4-5 ans. Compte-tenu de la population ciblee (osteoporose severe), il parait raisonnable d’aller au-dela d’un delai de 5 ans dans la plupart des situations.

Ostéoporose sévère: intérêt d'un suivi structural ?

Resume Les fractures vertebrales, localisations les plus frequentes de l’osteoporose, sont a l’origine d’une augmentation de la mortalite et ce, meme lorsqu’elles sont asymptomatiques. La presence d’une fracture prevalente, qu’elle soit radiologique ou clinique, predispose a la survenue de fractures incidentes chez les patientes non traitees, mais aussi chez les patientes traitees comme le montrent les etudes cliniques ou un suivi radiologique est fait systematiquement. Se pose donc la question d’un suivi structural systematique. La mesure de la taille est un 1 er outil pour le suivi et le depistage de nouvelles fractures vertebrales, mais reste peu specifique. Les radiographies ne peuvent etre faites de facon systematique en raison du cout et de l’irradiation. L’utilisation de la VFA (Vertebral Fracture Assessment) , peu irradiante et peu couteuse, realisee conjointement a l’osteodensitometrie, semble bien adaptee a un suivi des patientes presentant une osteoporose severe.