What is the name of the injection given every six months to patients with severe osteoporosis who are at risk of falling and have brittle bones?

Denosumab (Prolia®)

The injection you're referring to is denosumab (brand name Prolia®), administered as a 60 mg subcutaneous injection every 6 months for the treatment of severe osteoporosis in patients at high risk of fracture. 1

Mechanism and Administration

• Denosumab is a fully human monoclonal antibody that works by blocking RANKL (receptor activator of nuclear factor kappa-B ligand), which inhibits osteoclast formation and activity, thereby reducing bone resorption and increasing bone density 2

• The standard osteoporosis dose is 60 mg given subcutaneously every 6 months, making it convenient for patients who may have difficulty with daily or weekly oral medications 1, 3

Evidence for Fracture Reduction

• Denosumab has the strongest evidence among antiresorptive drugs for reducing fracture risk, including vertebral, non-vertebral, and hip fractures 3

• In postmenopausal women with osteoporosis, denosumab reduces:

  • Vertebral fractures by approximately 68% 4
  • Non-vertebral fractures by 20% 4
  • Hip fractures by approximately 40% 5

• The fracture reduction benefits are consistent across different patient subgroups, including those with varying ages, bone mineral density levels, and prior fracture history 4

Treatment Recommendations by Guidelines

For Severe Osteoporosis with High Fall Risk

• The American College of Physicians (2023) recommends bisphosphonates as first-line therapy, with denosumab as second-line treatment for patients who have contraindications to or experience adverse effects from bisphosphonates 3

• The American Society of Clinical Oncology (2019) states that denosumab at 60 mg every 6 months has the strongest evidence of benefit for reducing fracture risk among antiresorptive drugs 3

• The EULAR/EFORT guidelines (2017) recommend denosumab as an alternative for patients with oral intolerance, dementia, malabsorption, or non-compliance to oral bisphosphonates 3

For Glucocorticoid-Induced Osteoporosis

• The American College of Rheumatology (2017) conditionally recommends denosumab for adults ≥40 years at high or very high fracture risk on glucocorticoids, particularly when bisphosphonates are not appropriate 3, 6

Critical Safety Considerations

Rebound Vertebral Fractures

• CRITICAL WARNING: Discontinuing denosumab leads to rapid bone loss and a significant risk of multiple vertebral fractures starting approximately 7 months after the last injection 5, 2

• If denosumab must be stopped, immediate transition to bisphosphonate therapy within 6 months of the last dose is essential to prevent rebound fractures 6, 3

• The European Calcified Tissue Society specifically recommends using a bisphosphonate to reduce vertebral fracture risk upon stopping denosumab 3

Other Important Adverse Effects

• Osteonecrosis of the jaw occurs in 1-2% of patients 6

  • Baseline dental examination is recommended before starting therapy 6
  • Maintain good oral hygiene throughout treatment

• Severe hypocalcemia risk, particularly in patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²) 6

  • Check intact parathyroid hormone, serum calcium, and vitamin D levels before initiating therapy in CKD patients 6
  • Ensure adequate calcium (1000-1200 mg/day) and vitamin D (600-800 IU/day) supplementation 1, 3

• Atypical femoral fractures have been reported, though less commonly than with long-term bisphosphonate use 2

Bone Density Improvements

• Denosumab significantly increases bone mineral density at all skeletal sites 3, 1:

  • Lumbar spine: approximately 5-6% increase
  • Total hip: approximately 2-3% increase
  • Femoral neck: approximately 2% increase

• These BMD improvements are superior to or comparable with bisphosphonates and are maintained with continued therapy 3

Monitoring Requirements

• Unlike bisphosphonates, denosumab's effect is rapidly reversible, requiring strict adherence to the 6-month dosing schedule 5, 2

• Bone turnover markers should be monitored to assess treatment response and adherence 3

• DEXA scanning intervals of 1-2 years are recommended during treatment 6

Special Populations

Women of Childbearing Potential

• Denosumab should only be used in women not planning pregnancy and using effective contraception, as oral bisphosphonates are preferred due to better safety profile 3, 6

Patients with Chronic Kidney Disease

• Denosumab can be used in patients with severe renal impairment (unlike bisphosphonates which require dose adjustment or are contraindicated), but requires careful monitoring for hypocalcemia 6

Men with Osteoporosis

• Denosumab is FDA-approved and effective for men with osteoporosis, including those on androgen deprivation therapy for prostate cancer 1, 7

• Evidence shows similar BMD improvements and fracture reduction in men as in postmenopausal women 3, 1

Practical Considerations

• The subcutaneous route and 6-month dosing interval may improve adherence compared to oral bisphosphonates that require complex dosing instructions 7

• Cost is typically higher than generic oral bisphosphonates, which is why bisphosphonates remain first-line in most guidelines 3

• Denosumab is particularly useful for patients who cannot tolerate oral medications due to gastrointestinal side effects, esophageal disorders, or inability to remain upright for 30-60 minutes 3