Osteoporosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Raviteja Guddeti, M.B.B.S.[3]

Overview

The mainstays of treatment in primary osteoporosis disease are based on in life style modifications. Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary. Bisphosphonates are the first line treatment for osteoporosis disease. Raloxifene is the second line treatment of osteoporosis in postmenopausal women, for both treatment and prevention. Denosumab is a human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat Osteoporosis in elder men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal woman with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.

Osteoporosis medical therapy

• The mainstays of treatment in primary osteoporosis disease are based on change in life style, including:
  1. Fall avoidance
  2. Weight bearing exercises
  3. Adequate vitamin D and calcium consumption
• Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary.

Medical therapy purpose

• The primary most important goal for treatment of osteoporosis is to reduce longtime fracture risk in patients. Increasing bone mineral density (BMD) in response to the treatment is far less important than improvement of clinical aspects of osteoporosis, i.e., osteoporotic fracture. Therefore, most of the drugs' efficacy are measured by the extend they improve the fracture risk, in turn of increasing BMD.
• It has to explain for patients that treatment purpose is to reduce their fracture risk in the future. During the treatment, if a single fracture happened, it is not necessarily reflect of treatment failure; despite the major complicates fractures that may need to start alternative treatments or patient referral to specialist.
• Calcium and vitamin D supplementation have been found to be effective in reducing the long term fracture risk, significantly. In order to suggest the people to use vitamin D and calcium supplements, first the physician has to become sure that patient is not able to obtain the nutrients through daily intake. The available supplemental ions of calcium include calcium carbonate and calcium citrate; and vitamin D3 has various dosage forms.

Medical therapy candidates

• The national osteoporosis foundation (NOF) declare that osteoporosis treatment has to prescribed for followings:
  1. Elder men and postmenopausal women with past history of osteoporotic fracture
  2. Elder man and postmenopausal women with BMD-identified osteoporosis (T-score ≤ -2.5 SD)
  3. Elder man and postmenopausal women with -1.0 > T-score > -2.5 SD with high risk of osteoporotic fracture
  4. Men with hypogonadism that testosterone therapy is contraindicated

Medical therapy options

Bisphosphonates

Bisphosphonates are the first line treatment for osteoporosis disease. They are not indicated in people with severe renal function impairment; thus, it is important to check renal function and serum creatinine before prescription. These drugs have to taken orally with large amount of water, not laying down until two hours following consumption, due to high risk of esophagitis. Rare but serious side effects may include osteonecrosis of the jaw and atypical femoral fractures.

• Alendronate: it is frequently used to treat osteoporosis in men, postmenopausal women, and also in corticosteroid-induced osteoporosis.
  • The dosing is 70mg weekly per oral.
  • Alendronate reduces hip, vertebral, and non-vertebral osteoporotic fractures.
• Risedronate: it is also used to treat Paget's disease. Risedronate decreases the bone mass loss. Also available in delayed release forms.
  • The dosing is 35mg weekly or 150mg monthly per oral.
  • Risedronate reduces vertebral fractures.
• Ibandronate: it is used to treat osteoporosis only in postmenopausal women.
  • The dosing is 150mg monthly per oral; or 3mg every 3 months through intravenous (IV) rout.
  • Regarding that Ibandronate only reduced vertebral fractures and there is no evidence of non-vertebral fractures improvement, it is rarely prescribed.
• Zoledronic acid: it is also used for bone destructions due to Paget's disease, multiple myeloma, and metastatic bone tumors. Most potent bisphosphonate that has a higher risk of osteonecrosis of the jaw.
  • The dosing is 5mg annually through IV route.
  • Zoledronate reduces hip, vertebral, and non-vertebral osteoporotic fractures. Common adverse effects are flu-like symptoms and bone pain, especially presented with first dose.

Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor

• Denosumab: human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat Osteoporosis in elder men and postmenopausal women.
  • The dosing is 60mg subcutaneous every 6 months.
  • Denosumab reduces hip, vertebral, and non-vertebral osteoporotic fractures.
  • The major side effects are eczema and nausea.
• Romosozumab: human monoclonal antibody designed to sclerostin, blocking protein of canonical Wnt signaling bone formation pathway. It is used to prevent osteoporotic fractures in postmenopausal women.
  • The dosing is 210mg subcutaneous monthly.
  • Romosozumab reduces vertebral fractures.

Selective estrogen receptor modulator (SERM)

• Raloxifene: it is the second line treatment of osteoporosis in postmenopausal women, for both treatment and prevention.
  • The dosing is 60mg daily per oral. Raloxifene reduces vertebral fractures up to 35%.
  • The major side effects are DVT and hot flashes in young pre-menopausal women.
  • It has shown efficacy in reducing the prevalence and incidence of invasive breast cancer, too.

Parathyroid hormone and related peptide analogs

• Teriparatide: human recombinant parathyroid hormone used to treat postmenopausal woman with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.
• Usually, it is used in patients who cannot tolerate the oral bisphosphonates.
  • It is also approved for corticosteroid induced osteoporosis.
  • The dosing is 20mcg subcutaneous daily, approved for less than 2 years use.
  • Teriparatide reduces vertebral and non-vertebral fractures, but not reduced hip fracture.
  • Common side effects include nausea, hypercalcemia, and hypercalciuria. However, patients with previous radiation therapy, paget's disease, or young patients should avoid this medication.
• Abaloparatide: human recombinant parathyroid hormone used to treat postmenopausal woman with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.
  • It has a shorter duration of action than teriparatide.
  • The dosing is 80mcg subcutaneous daily, approved for less than 2 years use.
  • Abaloparatide reduces vertebral and non-vertebral fractures.
  • Common side effects are dizziness, headache, hypercalcemia, and hypercalciuria.

Calcitonin

• Calcitonin is a hormone that inhibit the function of osteoclasts and result in growing bone mass. On the other hand, it can stimulate the osteoblast and also inhibit sclerostin production.
• It is used for postmenopausal women with osteoporosis.
• The dosing is 100units subcutaneous daily; or 200units intranasal daily.
• Calcitonin reduces vertebral fractures up to 30%. Common side effects are rhinitis, nausea, and flushing.