Controversies in the treatment of postmenopausal osteoporosis: How long to treat with bisphosphonates?

Abstract

Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.

Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics

“…Patients treated with strong anti-resorptive agents are occasionally advised to stop taking those agents before and after invasive dental treatment such as tooth extraction due to the risk of ONJ development 42 . However, discontinuation of anti-resorptive agents reportedly reduces bone mass and may increase risk of fragility fractures in patients 43 , 44 . Our data indicate that ONJ development initiated by zoledronate treatment and tooth extraction is inhibited by either active vitamin D analogues, anti-inflammatory agents or antibiotics, even in the presence of zoledronate treatment.…”

Definition and management of very high fracture risk in women with postmenopausal osteoporosis: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Association of Bone Assessment and Metabolism (ABRASSO)

“…Over the last decades, most patients requiring pharmacological intervention were offered antiresorptive drugs as first-line therapy, whereas anabolic agents were considered as last resource for those with therapeutic failure. Although bisphosphonates continue to be the first-line agents for long-term pharmacological therapy in high-risk patients ( 15 ), recent randomized trials comparing bone-forming agents with bisphosphonates have shown that anabolic agents reduce fractures to a greater extent than antiresorptive agents in patients with severe osteoporosis ( 16 , 17 ). Additionally, it became apparent that the reduction in fracture risk may be more pronounced when patients are treated with anabolic agents first, followed by an antiresorptive drug ( 18 , 19 ).…”

Association between NF-κB Signal Pathway-Related Gene Polymorphisms and Response to Alendronate Treatment in Postmenopausal Chinese Women with Low Bone Mineral Density

“…Pain, fracture, and spinal deformity are the most common symptoms. With the aggravating trend of an aging population worldwide, osteoporosis is becoming a global public health issue and one of the leading causes of disability and death [ 5 , 6 ] in older individuals.…”

“…Bisphosphonates are efficient osteoclast inhibitors that help to restore the equilibrium between bone resorption and creation. Although bisphosphonate medication can increase BMD and lower the incidence of fracture [ 5 , 11 , 12 ], there are still individual differences in drug efficacy. Because genetic variables may explain this occurrence, identifying the indications for bisphosphonate therapy from gene targeting is of tremendous therapeutic importance.…”