Treatment failure in osteoporosis: What can be done?
Treatment failure in osteoporosis remains a problem, even among patients who are treatment-adherent, according to a presentation at the recent meeting of the Asian Federation of Osteoporosis Societies (AFOS 2017), held in Kuala Lumpur, Malaysia.
“The fundamental purpose of osteoporosis treatment is to reduce the risk of fracture. Available effective treatments only reduce fracture incidence by 20–60 percent, thus fractures do occur during treatment,” presented Professor Yang Rong-Sen from the National Taiwan University and Hospital, Taipei, Taiwan. [AFOS 2017, abstract SA5.1]
While multiple factors contribute to fractures, some patients may still experience failure with available treatment despite high compliance. Medication cannot treat everything, he said.
“Bisphosphonates [for example] improve some bone biomechanical parameters, but not non-skeletal risk factors for fracture such as falls, genotype, comorbidity, … and advanced age,” he said.
According to Yang, the International Osteoporosis Foundation (IOF) Inadequate Responders Working Group defined treatment failure as, after excluding secondary osteoporosis or maximal treatment adherence, ≥2 incident fragility fractures; or one incident fracture accompanied by elevations in the serum levels of the biomarkers C-telopeptide of type I collagen (CTX) or procollagen type I N propeptide (PINP) at baseline with no significant reduction during treatment or a significant decrease in bone mineral density (BMD) or both; or no significant decrease in serum CTX or PINP but a significant decrease in BMD. In these situations, the Working Group recommended a change of treatment. [Osteoporosis Int 2012;23:2769-2774]
If the patient is not meeting good response criteria within a year of treatment initiation, treating physicians should ensure that the patient is compliant and rule out occult secondary osteoporosis, said Yang. Following this, the IOF Working Group suggests treatment modifications such as replacing a weaker antiresorptive agent with a stronger one from the same class, replacing an oral drug with an injectable one, or replacing a strong antiresorptive agent with an anabolic agent. Nonetheless, choice of substituted medication following treatment failure would differ from one drug to another, said Yang. [Osteoporosis Int 2012;23:2769-2774]
Risk factors for treatment failure
Risk factors for treatment failure vary according to patient, as well as by medication type. In a retrospective study of patients with rheumatoid arthritis and osteoporosis, nonadherence to bisphosphonates was the main risk factor for treatment failure, followed by daily glucocorticoid dosage ≥7.5 mg/day prior to first BMD measurement, immobilization for >3 months, and DAS28* ≥3.2. [Mod Rheumatol 2016;26:194-199]
In the multinational, prospective observational GLOW** study, worse SF-36*** vitality score (OR per 10-point increase, 0.85; p=0.004), ≥2 falls in the past year (OR, 2.40; p=0.011), and prior fracture (OR, 2.93; p<0.0001) were predictors of treatment failure, defined in this study as ≥2 fractures while on antiosteoporosis medication. [J Bone Miner Res 2014;29:260-267]
In a retrospective study of individuals with osteopenia or osteoporosis, prior bisphosphonate or vitamin D use (odds ratio [OR], 1.50 each; p<0.05) were risk factors for teriparatide treatment failure, as determined by BMD change. However, there were no significant predictors of treatment failure when using fracture as the endpoint. [Bone Rep 2015;4:17-22]
In a study of postmenopausal women with previously untreated primary osteoporosis and at high risk for fractures, current smokers and those with baseline alkaline phosphatase total activity levels ≥66.5 U/L were at elevated risk of bisphosphonate treatment failure (OR, 3.22; p=0.034 and OR, 4.22; p=0.007, respectively). [Osteoporosis Int 2014;25:1401-1410]
Future research goals
In order to address treatment failure, the causes of treatment failure need to be determined, and new fractures, BMD, and bone turnover markers should be treated, said Yang, who advocated for more research into determining the factors behind treatment failure.
Among the causes of treatment failure are poor bone responders, inappropriate treatment, poor compliance, medication inefficacy, and fall-related injuries, he said.
“We still need a consensus on treatment failure,” said Yang. “[With the consensus], we may be able to detect true inadequate responders to osteoporosis treatment, identify possible associated factors in individual patients, act on individual additional factors to improve outcomes, determine the intervention threshold, and choose the most suitable medication for a given patient. The goal is treat to target,” he said.
Integrated approaches are necessary, said Yang, and referred to the use of a combined care approach such as an ortho-geriatric approach, as well as fracture liaison services in Taiwan.
We could also develop treat-to-target and fall prevention strategies for individual patients and assess and act on clinical risk factors. Importantly, we need to identify the real response and the effectiveness of initiating a new therapy, he said.