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.

Medical management

Medication

Bisphosphonates are the first line pharmacological measures for treatment of Osteoporosis. Other medications used are teriparatide and strontium ranelate. The national osteoporosis foundation recommendations for pharmacologic therapy include any post-menopausal women and men aged 50 and more who has the following features:

• a hip or vertebral fracture

• T-score of -2.5 or less on the DEXA scan at the femoral neck or spine after appropriate evaluation to exclude secondary causes

• T-score between -1.0 and -2.5 at the femoral neck or spine and a 10-year probability of a hip fracture of 3% or greater or a 10-year probability of a major osteoporosis-related fracture of 20% or greater. Medical therapy can only halt the progression of the disease but not cure it or reverse the pathological process.

• Bisphosphonates
  • Alendronate - approved for treatment in men, postmenopausal women and also in glucocorticoid induced osteoporosis. Clinical trials show positive results in the form of reduction of fractures in these patient populations. Usual dose is 70mg/week.
  • Risedronate - available in delayed release forms also. Dose is 35 mg/week
  • Zoledronic acid - most potent Bisphosphonate. It is a once a year intravenous infusion approved for the treatment of Osteoporosis in men, postmenopausal women and in glucocorticoid abuse. A study showed 35% reduction in hip fractures and more than 50% reduction in vertebral fractures after using this drug. This study also found a mortality benefit of 28%. But is nephrotoxic.
  • Ibandronate - this is a once a month oral bisphosphonate. I.V form is also available which is taken once in 3 months.

I.V route is preferred in patients who are intolerant to oral bisphosphonates and also n whom adherence is a issue. Precaution to be taken while taking bisphosphonates is that they have to be taken sitting upright with a large glass of water at least 30 minutes before eating in the morning.

A 2007 manufacturer-supported study suggested that in patients who had suffered a low-impact hip fracture, annual infusion of 5 mg zoledronic acid reduced risk of any fracture by 35% (from 13.9 to 8.6%), vertebral fracture risk from 3.8% to 1.7% and non-vertebral fracture risk from 10.7% to 7.6%. This study also found a mortality benefit: after 1.9 years, 9.6% of the study group (as opposed to 13.3% of the control group) had died of any cause, indicating a mortality benefit of 28%

Teriparatide

Recently, teriparatide (Forteo, recombinant parathyroid hormone residues 1–34) has been shown to be effective in osteoporosis. It is used mostly for patients with established osteoporosis (who have already fractured), have particularly low BMD or several risk factors for fracture or cannot tolerate the oral bisphosphonates. It is given as a daily injection with the use of a pen-type injection device. Teriparatide is only licensed for treatment if bisphosphonates have failed or are contraindicated (however, this differs by country and is not required by the FDA in the USA. However, patients with previous radiation therapy, or Paget's disease, or young patients should avoid this medication).

Strontium ranelate

Oral strontium ranelate is an alternative oral treatment, belonging to a class of drugs called "dual action bone agents" (DABAs) by its manufacturer. It has proven efficacy, especially in the prevention of vertebral fracture. In laboratory experiments, strontium ranelate was noted to stimulate the proliferation of osteoblasts, as well as inhibiting the proliferation of osteoclasts.

Strontium ranelate is taken as a 2 g oral suspension daily, and is licenced for the treatment of osteoporosis to prevent vertebral and hip fracture. Strontium ranelate has side effect benefits over the bisphosphonates, as it does not cause any form of upper GI side effect, which is the most common cause for medication withdrawal in osteoporosis. In studies a small increase in the risk of venous thromboembolism was noted,suggesting it may be less suitable in patients at risk for thrombosis for different reasons.

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, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (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 D

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 bearing, 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.