Drug holiday for osteoporosis: Who, when, how long?
Bisphosphonates have proven antifracture efficacy and remain to be the cornerstone of osteoporosis treatment. However, a drug holiday is of particular importance with bisphosphonates due to some signals with long-term use of the drug, including rare incidence of atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ), says a leading endocrinologist at AFOS 2017.
This raises questions on the need for intermittent discontinuation of bisphosphonate treatment after long-term use. The European Medical Association (EMA), in its position statement published this year, specifies that discontinuation of bisphosphonates should be considered in all patients with osteoporosis after >5 years of treatment with alendronate, risedronate or zoledronic acid, said Professor Leilani Mercado-Asis from the University of Santo Tomas, Manila, Philippines. “If the patient has not had fractures before or during therapy and the fracture risk is low, a drug holiday can be recommended.”
However, if a new fracture is experienced or a fracture risk has increased, and BMD remains low (femoral neck T-score ≤-2.5), anti-osteoporotic treatment should be resumed, she added.
The human IgG2 monoclonal antibody denosumab also has a good antifracture efficacy. “In cases of denosumab discontinuation, close monitoring is suggested due to the possibility of rebound fractures,” said Mercado-Asis.
Meanwhile, the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group advises clinicians managing patients with osteoporosis to individualize treatment decisions based on risk factors such as bone density, clinical risk factors, and history of incident fractures. The group, however, could not agree on the duration of holiday and how to monitor treatment once on a drug holiday. [Osteoporos Int 2016;27:849]
As responses to antiresorptive effects differ among Asians vs Caucasians, South Korea issued a position statement which states that drug holiday may be considered after 5 years of alendronate and risedronate treatment, and after 3 years of zoledronic acid in individuals who are not at high risk of fracture. However, treatment should be continued in patients at high fracture risk. Annual bone mineral density (BMD) monitoring is recommended during drug holiday. If there are significant reductions in BMD, or if T score reaches <2.5, or new osteoporotic fractures occur, bisphosphonate treatment may be restarted. Alternative therapy may be used for individuals at high risk of fractures. [J Bone Metab 2015; 22:167-174]
Drug of choice for osteoporosis fractures
“To put this into proper perspective, bisphosphonates, in my opinion, remain to be the drug of choice for prevention and treatment of osteoporosis fractures,” said Mercado-Asis. “The primary action of bisphosphonates is hitting an important physiological mechanism – bone remodeling – which is crucial in maintaining bone strength and durability.”
AFF and ONJ, though rare, are apparent side effects that are causing realistic concerns, she added. “Drug holiday remains controversial and are subject to debates. Individualizing treatment regimen according to the degree of risks is of immense value. Instead of stopping bisphosphonates, should we consider alternative treatment?”