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

Drugs, especially bisphosphonates are the main medications in the treatment of osteoporosis. However, lifestyle changes are also emphasized. No treatment can completely reverse established osteoporosis. Medical management can only halt the progression of the disease process.

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 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. The dosing is 35mg weekly or 150mg monthly per oral. Also available in delayed release forms. The drug 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 jaw. The dosing is 5mg annually through IV route. Zolendronate 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 treatOsteoporosis 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. 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:

• Calcitonin - Calcitonin-salmon is a hormone that decreases osteoclast function and therefore reducing impending bone loss. It is indicated for use only in women who are 5 years post-menopause and have a low bone mineral density. Clinical trials show a reduced vertebral fracture risk by 30%. Intra nasal spray and subcutaneous forms are available. 200 IU is the usual prescribed dose.

Nutrition

• Calcium - the patient should include 1200 to 1500 mg of calcium daily either via dietary means (for instance, an 8 oz glass of milk contains approximately 300 mg of calcium) or via supplementation. The body absorbs only about 500 mg of calcium at one time and so intake should be spread throughout the day. However, the benefit of supplementation of calcium alone remains, to a degree, controversial since several nations with high calcium intakes through milk-products (e.g. the USA, Sweden) have some of the highest rates of osteoporosis worldwide, though this may be linked to such countries' excess consumption of protein. A few studies even suggested an adverse effect of calcium excess on bone density and blamed the milk industry for misleading customers. Some nutritionists assert that excess consumption of dairy products causes acidification, which leaches calcium from the system, and argue that vegetables and nuts are a better source of calcium and that in fact milk products should be avoided. This theory has no proof from scientific clinical studies. Similarly, nutritionists believe that excess caffeine consumption can also contribute to leaching calcium from the bones.

A meta-analysis of randomized controlled trials concluded "Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older. For best therapeutic effect, recommended minimum dose calcium is 1200 mg, and of vitamin D is 800 IU (for combined calcium plus vitamin D supplementation)." A study that examined the relationship between calcium supplementation and clinical fracture risk in an elderly population, there was a significant decrease in fracture risk in patients that received calcium supplements versus those that received placebo. However, this benefit only applied to patients who were compliant with their treatment regimen.

• Vitamin - increasing vitamin D intake has been shown to reduce fractures up to twenty-five percent in older people, according to recent studies.. The very large Women's Health Initiative study, however, did not find any fracture benefit from calcium and vitamin D supplementation, but these women were already taking (on average) 1200 mg/day of calcium . Muscle weakness can contribute to falls so it is beneficial for people living with osteoporosis to improve muscle function. Vitamin D deficiency causes muscle weakness.. A meta-analysis of five clinical trials showed 800 IU of vitamin D per day (plus calcium) reduced the risk of falls by 22%.. A different randomized, controlled study showed nursing home residents who took 800 IU of vitamin D per day (plus calcium) having a 72% reduction in the risk of falls.. New vitamin D intake recommendations (National Osteoporosis Foundation, July 2007) are adults up to age 50, 400-800 IU daily and those over 50, 800 - 1,000 IU daily.

• Excess protein - there are three elements relating to a person's levels of calcium: consumption, absorption, and excretion. High protein intake is known to encourage urinary calcium losses and has been shown to increase risk of fracture in research studies..

• Others - There is some evidence to suggest bone density benefits from taking the following supplements (in addition to calcium and vitamin D): boron, magnesium, zinc, copper, manganese, silicon, strontium, folic acid, and vitamins B6, C, and K. This is weak evidence and quite controversial.

Exercise

• Multiple studies have shown that aerobics, weight lifting, and resistance exercises can all maintain or increase BMD in postmenopausal women.
• Many researchers have attempted to pinpoint which types of exercise are most effective at improving BMD and other metrics of bone quality, however results have varied. One year of regular jumping exercises appears to increase the BMD and moment of inertia of the proximal tibia in normal postmenopausal women.

• Treadmill walking, gymnastic training, stepping, jumping, endurance, and strength exercises all resulted in significant increases of L2-L4 BMD in osteopenic postmenopausal women.

• Strength training elicited improvements specifically in distal radius and hip BMD.