title: Postmenopausal osteoporosis treatment with antiresorptives: effects of discontinuation or long-term continuation on bone turnover and fracture risk--a perspective.
abstract: Osteoporosis may be a lifelong condition. Robust data regarding the efficacy and safety of both long-term osteoporosis therapy and therapy discontinuation are therefore important. A paucity of clinical trial data regarding the long-term antifracture efficacy of osteoporosis therapies necessitates the use of surrogate endpoints in discussions surrounding long-term use and/or discontinuation. Long-term treatment (beyond 3-4 years) may produce further increases in bone mineral density (BMD) or BMD stability, depending on the specific treatment and the skeletal site. Bisphosphonates, when discontinued, are associated with a prolonged reduction in bone turnover markers (BTMs), with a very gradual increase to pretreatment levels within 3 to 60 months of treatment cessation, depending on the bisphosphonate used and the prior duration of therapy. In contrast, with nonbisphosphonate antiresorptive agents, such as estrogen and denosumab, BTMs rebound to above pretreatment values within months of discontinuation. The pattern of BTM change is generally mirrored by a more or less rapid decrease in BMD. Although the prolonged effect of some bisphosphonates on BTMs and BMD may contribute to residual benefit on bone strength, it may also raise safety concerns. Adequately powered postdiscontinuation fracture studies and conclusive evidence on maintenance or loss of fracture benefit is lacking for bisphosphonates. Similarly, the effects of rapid reversal of bone turnover upon discontinuation of denosumab on fracture risk remain unknown. Ideally, studies evaluating the effects of long-term treatment and treatment discontinuation should be designed to provide head-to-head "offset" data between bisphosphonates and nonbisphosphonate antiresorptive agents. In the absence of this, a clinical recommendation for physicians may be to periodically assess the benefits/risks of continuation versus discontinuation versus alternative management strategies.
authors.affiliation: Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Serge
authors.initials: S
authors.lastname: Ferrari
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.forename: Erik F
authors.initials: EF
authors.lastname: Eriksen
authors.forename: Philip N
authors.initials: PN
authors.lastname: Sambrook
authors.forename: Juliet
authors.initials: J
authors.lastname: Compston
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000188:drug therapy*; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D012307:Risk Factors; D013995:Time
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates