Bone health

No drug holidays with bisphosphonates: Osteoporosis Australia

Long term treatment of osteoporosis with anti-resorptive drugs such as bisphosphonates should not be paused because of concerns over rare adverse events such as atypical fractures, a new position statement from Osteoporosis Australia recommends.

While some guidelines have suggested that a two year ‘drug holiday’ may be taken after five years of bisphosphonate therapy, the Osteoporosis Australia advice aimed at GPs is that treatment should not be stopped because this will lead to further loss of bone mass and microarchitectural deterioration.

“If treatment is initiated, for the majority of patients it should be permanent (lifelong) because …  any antiresorptive therapy slows, but does not reverse, the destruction of bones [and] stopping treatment results in recurrence of bone loss,” it says.

“The loss of benefits is very rapid with drugs like denosumab, intermediate with menopausal hormone therapy (MHT) or the orally administered bisphosphonates, and slow with other drugs like zoledronic acid. For these reasons, stopping treatment is generally not recommended.”

The advice is among eight recommendations based on a National Forum of clinical experts hosted by Osteoporosis Australia (OA) in March 2019.

They concluded that for most patients who have sustained a fragility fracture or are over the age of 70 and have low bone mineral density, “the benefits of therapy in reducing risk of fracture should strongly outweigh the risks of rare adverse events such as osteonecrosis of the jaw or atypical femur fractures that may be associated with long-term therapy.”

The Key Messages are:

  1. Osteoporosis is a chronic disease and like other chronic diseases needs long-term treatment over a lifetime in most cases.
  2.  If osteoporosis treatment is interrupted in patients attaining a lower fracture risk, patients must be reviewed with bone density tests, bone remodelling markers and clinical follow-up for new fractures or emerging causes for bone fragility. Bone loss will eventually restart and the benefits of treatment will be lost.
  3. There is no treatment interruption with denosumab, as its effects are rapidly reversible. If, for whatever reason denosumab treatment cannot be continued, transition to an oral bisphosphonate for at least 12 months is recommended, commencing within 4 weeks of the missed dose.
  4. In all Australians aged >70 years and in most Australians aged >50 years with a fragility fracture, a bone density test is recommended.
  5. If a patient has a fracture during treatment this may indicate a need to change therapy, specialist consultation may be required.
  6. The transition from denosumab to the anabolic drug, teriparatide, may be associated with bone loss.
  7. A BMD T score ≤ -2.5 is diagnostic of osteoporosis and bone fragility. However, in younger patients with a T score of ≤ -2.5, the absolute fracture risk may not exceed the intervention threshold.
  8. As fracture risk also depends on age and other clinical risk factors (e.g. glucocorticoid use) in addition to the BMD T score, an absolute fracture risk calculator (FRAX®or Garvan) is useful to calculate this risk over the next 5 or 10 years. If the 10-year risk of any fragility or hip fracture is >20% or >3%, respectively, treatment is recommended.

In contrast, RACGP recommendations for bisphosphonate treatment of osteoporosis suggest that clinicians “reconsider the need to continue bisphosphonate therapy after 5–10 years in postmenopausal women and men over the age of 50 with osteoporosis who have responded well to treatment (T-score ≥–2.5 and no recent fractures).”

“If BMD remains low (T-score ≤–2.5) and/or there are incident vertebral fractures, continue treatment. Treatment should be restarted if there is evidence of bone loss, especially at the hip, or if a further minimal trauma fracture is sustained,” they advise.

The American Society for Bone and Mineral Research in its recommendations on long term bisphosphonate treatment suggests that reassessment of risk should be considered after five years of oral bisphosphonate or three years of intravenous bisphosphonate.

“In women at high risk, for example, older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture, or who fracture on therapy, continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered.”

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