What are the latest drugs available for the treatment of osteoporosis, including their mechanism of action, dosages, and pros and cons?

From the Guidelines

The latest drugs for osteoporosis treatment include antiresorptive medications such as bisphosphonates (alendronate, risedronate, ibandronate, and zoledronic acid) and denosumab, as well as anabolic agents like teriparatide, abaloparatide, and romosozumab, which help maintain bone density and reduce fracture risk. These medications have different mechanisms of action, dosages, and pros and cons. Antiresorptive medications like bisphosphonates inhibit osteoclast activity to slow bone breakdown, while denosumab prevents osteoclast formation by inhibiting RANKL 1. Anabolic agents, on the other hand, stimulate bone formation, with teriparatide and abaloparatide being PTH analogs, and romosozumab being a sclerostin inhibitor that increases bone formation and decreases resorption 1. The dosages for these medications vary, with alendronate typically given at 70mg weekly, risedronate at 35mg weekly, ibandronate at 150mg monthly, and zoledronic acid at 5mg IV yearly. Denosumab is given as a 60mg subcutaneous injection every 6 months, while teriparatide and abaloparatide are given at 20mcg subcutaneous daily for up to 2 years, and romosozumab at 210mg subcutaneous monthly for 12 months. Some key points to consider when selecting a treatment include:

• The patient's fracture risk, with high-risk patients potentially benefiting from sequential therapy starting with an anabolic agent followed by an antiresorptive 1
• The patient's comorbidities, such as gastrointestinal issues or cardiovascular disease, which may affect the choice of medication
• Cost considerations, as some medications may be more expensive than others
• Patient preferences regarding administration route and frequency, with some patients preferring oral medications and others preferring injectable medications. It's also important to note that treatment selection should be individualized and based on the latest evidence, with the goal of maximizing bone formation and reducing fracture risk while minimizing potential side effects and complications. Some potential side effects and complications to consider include gastrointestinal issues with oral bisphosphonates, rare but serious complications like osteonecrosis of the jaw or atypical femur fractures with long-term use, and potential osteosarcoma risk with teriparatide/abaloparatide, as well as cardiovascular risk with romosozumab 1.

From the FDA Drug Label

1.1 Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture 1.2 Treatment to Increase Bone Mass in Men with Osteoporosis 1.3 Treatment of Glucocorticoid-Induced Osteoporosis 1.4 Treatment of Bone Loss in Men Receiving Androgen Deprivation Therapy for Prostate Cancer 1.5 Treatment of Bone Loss in Women Receiving Adjuvant Aromatase Inhibitor Therapy for Breast Cancer 2.3 Recommended Dosage 12.1 Mechanism of Action

The drug denosumab (SQ) is used for the treatment of osteoporosis.

• Mechanism of action: Not explicitly stated in the provided text, but denosumab is known to be a RANKL inhibitor which prevents the formation, function, and survival of osteoclasts, leading to decreased bone resorption.
• Dosages: The recommended dosage is not specified in the provided text.
• Pros and cons:
  • Pros:
    • Effective in increasing bone mass and reducing the risk of fractures
  • Cons:
    • May cause severe hypocalcemia in patients with advanced kidney disease
    • May cause osteonecrosis of the jaw and atypical subtrochanteric and diaphyseal femoral fractures
    • May cause serious infections and dermatologic adverse reactions
    • May cause musculoskeletal pain and suppression of bone turnover 2

From the Research

Latest Drugs for Osteoporosis Treatment

The latest drugs available for the treatment of osteoporosis include:

• Bisphosphonates (e.g., alendronate, risedronate, zoledronic acid) 3, 4, 5
• Denosumab 3, 4
• Strontium ranelate 3
• Teriparatide 3

Mechanism of Action

The mechanism of action of these drugs includes:

• Inhibition of osteoclastic bone resorption (bisphosphonates) 5
• Inhibition of RANKL, a protein that acts as the primary signal to promote bone resorption (denosumab) 4
• Stimulation of bone formation (teriparatide) 3
• Increase in bone mineral density (strontium ranelate) 3

Dosages

The dosages of these drugs vary:

• Alendronate: 70 mg once weekly or 10 mg once daily 3
• Risedronate: 35 mg once weekly or 5 mg once daily 3
• Zoledronic acid: 5 mg once yearly via intravenous infusion 3, 6
• Denosumab: 60 mg via subcutaneous injection every 6 months 4
• Strontium ranelate: 2 g once daily 3
• Teriparatide: 20 mcg once daily via subcutaneous injection 3

Pros and Cons

The pros and cons of these drugs include:

• Bisphosphonates:
  • Pros: proven antifracture efficacy, good safety profile 4, 5
  • Cons: potential for gastrointestinal side effects, osteonecrosis of the jaw 6
• Denosumab:
  • Pros: good antifracture efficacy, convenient dosing schedule 4
  • Cons: potential for hypocalcemia, long-term safety data lacking 4
• Strontium ranelate:
  • Pros: increases bone mineral density, reduces fracture risk 3
  • Cons: potential for cardiovascular side effects, limited long-term data 3
• Teriparatide:
  • Pros: stimulates bone formation, reduces fracture risk 3
  • Cons: potential for hypercalcemia, limited long-term data 3