Comparative Efficacy of Anabolic Therapies in Osteoporosis

Guideline-Based Treatment Positioning

The American College of Physicians recommends bisphosphonates as first-line treatment for primary osteoporosis (strong recommendation, high-certainty evidence) 1, 2
Romosozumab (Evenity) or teriparatide (Forteo) should be used only for females with primary osteoporosis at very high risk of fracture (conditional recommendation, low-certainty evidence for teriparatide) 1, 2
Very high risk typically includes: prior vertebral fracture, multiple fractures, low bone density, or fracture on osteoporosis therapy 1

Patients initially treated with anabolic agents must be offered an antiresorptive agent after discontinuation to preserve gains and prevent serious risk of rebound and multiple vertebral fractures 1, 2, 3, 4, 5
Transition to bisphosphonates or denosumab is mandatory 1, 5

Teriparatide may increase risk for serious adverse events and probably increases withdrawal due to adverse events 1, 2
Teriparatide is associated with hypercalcemia, gastrointestinal symptoms, headache, and hypercalciuria 6
No osteosarcoma cases linked to teriparatide in postmarketing surveillance 6

Must transition to antiresorptive therapy immediately after completion of anabolic therapy 1, 5
Never discontinue anabolic therapy without immediately starting antiresorptive therapy—this causes rapid bone density loss and rebound vertebral fractures 1, 5

Avoid using anabolic agents when patient is not at very high fracture risk—use bisphosphonates instead 1, 2
Avoid using anabolic agents when patient cannot commit to mandatory follow-on antiresorptive therapy 1, 5
Ensure calcium and vitamin D supplementation with either agent 5

The American College of Physicians recommends bisphosphonates as first-line therapy for osteoporosis, with Tymlos reserved only for females with primary osteoporosis at very high risk of fracture (conditional recommendation, low-certainty evidence for similar anabolic agents) 7
Tymlos should be reserved exclusively for patients at very high fracture risk—it is not a first-line treatment 7

In men with osteoporosis, Tymlos produces rapid and significant improvements in bone mineral density, and common adverse effects include injection site reactions, dizziness, arthralgia, nausea, diarrhea, and bone pain 7

The American College of Physicians recommends Tymlos and Forteo as second-line or third-line therapies for females with primary osteoporosis at very high fracture risk (conditional recommendation, low-certainty evidence) 8
Both agents require immediate transition to antiresorptive therapy (bisphosphonates or denosumab) after completion to preserve gains and prevent rebound vertebral fractures 8
Tymlos and Forteo may cause hypercalciuria, and measurement of urinary calcium excretion should be considered if active urolithiasis or pre-existing hypercalciuria is suspected 9
The National Kidney Foundation notes that both teriparatide and abaloparatide carry concerns for hypercalcemia and hyperuricemia in CKD patients 9
The National Kidney Foundation also notes that use of teriparatide in CKD G4-G5D is off-label 10
The American College of Physicians recommends ensuring calcium (1000-1200 mg/day) and vitamin D (600-800 IU/day) supplementation with either agent 8

The National Kidney Foundation notes that both teriparatide and abaloparatide carry concerns for hypercalcemia and hyperuricemia in CKD patients 10
Tymlos is approved for men with osteoporosis at high risk for fracture, producing rapid and significant BMD improvements, according to the Endocrine Society 8

The American College of Physicians notes that both agents are significantly more expensive than generic bisphosphonates 8
High acquisition cost means both should be reserved for patients at very high fracture risk or those who have failed/are intolerant to bisphosphonates, according to the American College of Physicians 8