27th February 2025

Management of osteoporosis

National guidance suggests that treatment can be given without BMD measurement in:

• Those with a history of a fragility fracture
• Patients with a high risk of fragility fracture, as suggested by a 10-year probability of a major osteoporotic fracture above the upper assessment threshold (estimated via FRAX score)

However, baseline BMD measurements are useful for comparison against future measurements. Those with an intermediate FRAX score should undergo BMD measurement via DXA scanning, with treatment offered if their updated FRAX score is greater than an age-specific intervention threshold.

Bisphosphonates

In most cases, first-line treatment involves oral bisphosphonates alongside lifestyle measures such as a healthy diet with sufficient calcium and vitamin D intake (or supplementation as necessary), smoking cessation, moderation of alcohol use, and regular weight-bearing exercises. While oral alendronate and risedronate are generally preferred, IV zoledronate is first-line following a hip fracture or in patients with pre-existing oesophageal disorders. Patients who suffer upper gastrointestinal side effects should be first trialled on an alternative oral bisphosphonate.

Patients receiving intravenous bisphosphonates should be notified of the risk of a transient flu-like illness, which infrequently recurs after the first injection and requires symptom management only. Other notable side effects for all bisphosphonates, though rare, include osteonecrosis of the jaw and atypical femoral fractures. The latter are often bilateral and associated with prodromal pain up to a few months before the fracture(s). Management involves cessation of bisphosphonate therapy, restriction of weight-bearing movements and orthopaedic review.

Patients on oral bisphosphonates whose FRAX ± BMD at 5-year reassessment does not warrant intervention may be considered for a 1.5-3 year pause (‘bisphosphonate holiday’) in an effort to maintain the balance between potential side effects and treatment benefit (as bisphosphonates are retained in bone for a prolonged period following cessation). However, patients who are currently on high-dose glucocorticoids, have a previous hip fracture or ≥2 vertebral fractures, or are over 70 years of age should be counselled for 10 years of treatment; although reassessment at 5 years is advised, most should continue for a further 5 years. Specialist opinion may need to be sought when considering whether to continue treatment beyond 10 years. Similar guidance applies to those on intravenous bisphosphonates, though reassessment is advised at 3 years rather than 5, with a full treatment course consisting of 6 years rather than 10.

Reassessment before 5 or 3 years is advised if risk factors change or a fracture occurs. Consideration of alternative treatments (i.e. treatment failure) is required if fracture occurs and there is a fall in BMD, or if there are two or more fractures while on treatment.

Other antiresorptive agents

The RANK ligand inhibitor denosumab is one alternative, but cessation is associated with an increased likelihood of vertebral fractures. To minimise this risk, IV zoledronate is recommended 6 months after the last dose, with further treatment guided by monitoring of the bone biomarker CTX-1 (C-terminal telopeptide of type I collagen, cleaved by osteoclasts during bone resorption).

Calcitriol (activated vitamin D) reduces vertebral fracture risk in postmenopausal women with osteoporosis, but requires baseline, 1 month, 3 month and then 6 monthly measurement of renal function and serum calcium levels.

The last antiresorptive agents include HRT and the selective oestrogen receptor modulator raloxifene (which has partial anabolic properties too). One mechanism through which oestrogens prevent bone demineralisation is stimulation of calcitonin, which inhibits osteoclastic activity. HRT specifically should be considered in women aged ≤60 years with a low background risk for the most serious of HRT’s side effects (increased cancer and thromboembolic risk). It should be noted that raloxifene has not been shown to reduce non-vertebral fractures.

Anabolic agents

Though persistent hyperparathyroidism is associated with osteoporosis, intermittent exposure to PTH results in greater stimulation of osteoblasts than it does osteoclasts; this is in part mediated by PTH’s downregulation of sclerostin, which inhibits osteoblasts. Teriparatide (a form of PTH) and romosozumab (a sclerostin inhibitor), therefore, act as anabolic agents. They are first-line in postmenopausal women at very high fracture risk, with teriparatide first-line in men ≥50 years at very high fracture risk and are particularly beneficial in patients with vertebral fractures. Once the treatment course for teriparatide or romosozumab expires (24 or 12 months respectively), an antiresorptive agent should be initiated.

Strontium ranelate

In severe osteoporosis, where neither antiresorptive nor anabolic drugs are appropriate in a postmenopausal woman or a man, the dual-acting drug strontium ranelate can be considered if the risk of fracture outweighs the increased risk of cardiovascular and thromboembolic events associated with the drug.