What is the role of Teriparatide (TBS) in the treatment of osteoporosis?

Role of Teriparatide in Osteoporosis Treatment

Teriparatide should be used only in postmenopausal women with primary osteoporosis at very high risk for fracture, followed by bisphosphonate therapy, and limited to 24 months of treatment. 1

Indications for Teriparatide

Teriparatide is indicated for specific populations with osteoporosis:

• Postmenopausal women with osteoporosis at high risk for fracture (defined as having a history of osteoporotic fracture or multiple risk factors for fracture) or who have failed or are intolerant to other available osteoporosis therapy 2
• Men with primary or hypogonadal osteoporosis at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy 2
• Men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture or who have failed or are intolerant to other available osteoporosis therapy 2

Efficacy and Mechanism of Action

Teriparatide is an anabolic (bone-forming) agent that works differently from antiresorptive therapies:

• Reduces risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis 2
• Increases bone formation through two distinct mechanisms:
  • Direct stimulation of bone formation within active remodeling sites and on previously inactive bone surfaces 3
  • Increases initiation of new remodeling sites 3
• Evidence shows teriparatide reduces risk for:
  • Any clinical fractures (ARD, 27 fewer events per 1000 patients; high certainty) 1
  • Radiographic vertebral fractures (ARD, 69 fewer events per 1000 patients; high certainty) 1
  • Clinical vertebral fractures (ARD, 45 fewer events per 1000 patients; low certainty) 1
• May not significantly reduce risk for hip fractures (low certainty evidence) 1

Patient Selection Criteria

Teriparatide should be reserved for specific patients:

• Postmenopausal women with very high risk for fracture 1
• Very high risk is defined as:
  • Older age (mean age >74 years in clinical trials) 1
  • Recent fracture (within past 12 months) 1
  • History of multiple clinical osteoporotic fractures 1
  • Multiple risk factors for fracture 1
  • Failure of other available osteoporosis therapy 1
• Typically used as a third-line therapy after failure of first-line (bisphosphonates) and second-line (denosumab) treatments 1

Treatment Duration and Follow-up

Treatment with teriparatide has important time limitations:

• Limited to 24 months maximum during a patient's lifetime 2, 3
• Discontinuation of teriparatide results in rapid bone loss and higher fracture risk 1
• Must be followed by an antiresorptive agent (typically a bisphosphonate) to maintain bone gains 1, 3
• The full continuous 24-month course provides better skeletal health outcomes than shorter treatment periods 3

Adverse Effects

Teriparatide has several important side effects to consider:

• May not increase risk of serious adverse effects (low certainty) 1
• Probably increases risk for withdrawal due to adverse effects (moderate certainty) 1
• Common adverse effects include nausea, dizziness, vomiting, headache, palpitations, and leg cramps 1
• Increased risk for withdrawal due to adverse events in the longer term (36 months) (risk ratio 3.1; low certainty) 1
• Osteosarcoma risk: Increased incidence observed in rat studies but not in human observational studies 2

Comparison with Other Treatments

When considering teriparatide versus other osteoporosis treatments:

• Compared with bisphosphonates at 24-month assessment:
  • Probably reduced risk for radiographic vertebral fractures (ARD, 66 fewer events per 1000 patients; moderate certainty) 1
  • May reduce risk for any clinical fracture (ARD, 46 fewer events per 1000 patients; low certainty) 1
  • May result in no differences in serious adverse events (low certainty) 1
• Bisphosphonates remain first-line therapy due to more favorable balance among benefits, harms, patient values and preferences, and cost 1
• Denosumab is suggested as second-line treatment for those with contraindications to bisphosphonates 1

Practical Considerations

When prescribing teriparatide:

• Administered as 20 mcg subcutaneous injection once daily 2
• Patients should take supplemental calcium and vitamin D if daily dietary intake is inadequate 2
• Monitor for hypercalcemia, especially after first month of treatment 2
• Patients may experience orthostatic hypotension, particularly with initial doses 2
• Cost is significantly higher than other osteoporosis treatments 4, 5

Contraindications

Teriparatide should not be used in patients with:

• Hypersensitivity to teriparatide or any of its excipients 2
• Open epiphyses (pediatric and young adult patients) 2
• Bone metastases or history of skeletal malignancies 2
• Metabolic bone diseases other than osteoporosis 2
• Pre-existing hypercalcemia 2