What is the recommended duration of treatment with Prolia (denosumab)?

From the Guidelines

Prolia (denosumab) should be taken for up to 2 years, with continuation beyond 2 years based on clinical judgement, as recommended by the NCCN Guidelines for multiple myeloma 1. The standard regimen for Prolia is one 60 mg injection given under the skin every six months. Most patients continue Prolia treatment for many years as stopping the medication can lead to rapid bone loss and increased fracture risk.

• The NCCN Guidelines for multiple myeloma recommend bisphosphonates (category 1) or denosumab for all patients receiving therapy for symptomatic multiple myeloma regardless of documented bone disease 1.
• Denosumab is preferred by the NCCN Panel in patients with renal disease 1.
• A recent meta-analysis of 20 randomized controlled trials comparing bisphosphonates with either placebo or a different bisphosphonate as a comparator concluded that adding bisphosphonates to the treatment of multiple myeloma reduces vertebral fractures and probably reduces pain 1.
• The frequency of dosing (monthly vs every 3 months) would depend on the individual patient criteria and response to therapy 1.
• It is essential to take calcium and vitamin D supplements as directed by your doctor, have regular bone density tests, and attend follow-up appointments to monitor your response to treatment while on Prolia.
• Always consult with your healthcare provider before making any changes to your Prolia treatment schedule. The ESMO clinical practice guidelines also recommend denosumab or zoledronate in patients with multiple myeloma and bone metastases, whether they are symptomatic or not 1.
• Denosumab should be administered every 4 weeks, and extending intervals beyond this frequency cannot currently be recommended 1.
• Discontinuation of treatment after an arbitrary duration other than perhaps for those patients with oligometastatic bone disease in disease remission is not recommended 1.

From the FDA Drug Label

2.3 Recommended Dosage Prolia should be administered by a healthcare professional. The recommended dose of Prolia is 60 mg administered as a single subcutaneous injection once every 6 months. Administer Prolia via subcutaneous injection in the upper arm, the upper thigh, or the abdomen All patients should receive calcium 1000 mg daily and at least 400 IU vitamin D daily [see Warnings and Precautions (5.1)]. If a dose of Prolia is missed, administer the injection as soon as the patient is available. Thereafter, schedule injections every 6 months from the date of the last injection.

The duration of treatment with Prolia is not explicitly stated in the provided drug labels. However, it is recommended to administer Prolia every 6 months.

• Key points:
  • Prolia should be administered every 6 months.
  • If a dose is missed, it should be administered as soon as possible, and then every 6 months thereafter.
  • The labels do not provide information on the maximum duration of treatment or when to stop treatment. 2

From the Research

Duration of Prolia Treatment

The duration of Prolia (denosumab) treatment can vary depending on the individual's condition and response to the medication.

• According to a study published in 2018 3, denosumab has been shown to be effective in reducing the risk of vertebral, nonvertebral, and hip fractures, and increasing bone mineral density (BMD) across skeletal sites, with benefits maintained over up to 10 years of therapy.
• Another study published in 2023 4 found that teriparatide and denosumab were superior to bisphosphonates in increasing BMD, with denosumab showing a mean difference of 2.07% in lumbar vertebrae BMD.
• A 2019 meta-analysis 5 compared denosumab and bisphosphonates in patients with osteoporosis and found that denosumab increased BMD more than bisphosphonates at 12 and 24 months, with a lower osteoporotic fracture incidence at 24 months.
• A 2022 systematic review and meta-analysis 6 compared denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis and found that denosumab was superior to bisphosphonates in improving BMD in lumbar spine and ultra-distal radius.
• A 2025 study 7 found that bisphosphonates maintained BMD after sequential teriparatide and denosumab in premenopausal women with idiopathic osteoporosis, with no new vertebral or nonvertebral fractures occurring.

Key Findings

• Denosumab has been shown to be effective in reducing the risk of fractures and increasing BMD over a period of up to 10 years 3.
• The medication is typically administered via subcutaneous injection once every 6 months 3.
• Denosumab has been compared to bisphosphonates in several studies, with varying results 4, 5, 6.
• The duration of treatment with denosumab may depend on individual factors, such as response to treatment and presence of side effects.