FRAX™ is a tool available online (http://​www.​shef.​ac.​uk/​FRAX/​index.​htm) which was developed by the World Health Organization. It is employed to gather independent risk factors for osteoporotic fractures involving individuals over 50 years of age, in order to quantify the probability of fracture of the femoral neck or other major osteoporotic fractures (vertebral, hip, forearm, and humerus) over the following 10 years.

The variables considered include gender, age, BMI, personal history of fractures after the age of 40, family history of hip fractures, smoking, excessive alcohol consumption, rheumatoid arthritis, use of glucose-corticoids, or other secondary causes of osteoporosis [5].

Using population samples from Europe, North America, Asia, and Australia, country-specific data was compiled, allowing calculations based on regional differences. When FRAX is associated with bone mineral density (BMD) testing, it is a more useful tool for predicting fracture risk than the use of either FRAX or BMD alone.

Although its use is not routinely indicated for patients who are already being treated for osteoporosis, a recent study demonstrated that FRAX may be a useful tool for assessing fracture risk in these patients, pointing to the need to either continue or discontinue medication [6].

There are three main components in the non-pharmacologic therapy of osteoporosis: diet, exercise, and the cessation of smoking. In addition, the patient should also avoid drugs that increase bone loss, such as glucose-corticoids.

There are several medications that can be used in the treatment of osteoporosis. The main medications employed are reviewed below (Table 24.4).

Using calcitonin for the treatment of osteoporosis, a study that included 5 years of follow-up with 1,255 women with T-scores of less than −2 (lumbar spine and at least one vertebral fracture), randomly assigned either a placebo or doses of 100, 200 or 400 IU/day of intranasal calcitonin. A small and inconsistent beneficial effect on the vertebral BMD from nasal calcitonin treatment was found, and included a reduction in the risk of vertebral fractures [25].

Data on the effect of calcitonin in locations other than the spinal column are conflicting.

A recent meta-analysis with heterogeneous results, using a limited number of patients, showed calcitonin to be of benefit for the short-term relief of acute pain (less than 10 days) in patients who have suffered a vertebral fracture. In contrast, calcitonin has not proved to be effective for patients with chronic pain (over 3 months) [26].

Bisphosphonates are synthetic analogues of pyrophosphate in which the oxygen bridge is replaced by a carbon atom [38]. They suppress bone resorption mediated by osteoclasts through a mechanism different from other anti-resorptive agents, binding to hydroxyapatite on bone surfaces, particularly those undergoing active resorption. When the osteoclasts begin to reabsorb bone that is impregnated with bisphosphonate, the bisphosphonate released during resorption impairs the ability of osteoclasts to form the wrinkled edge needed to adhere to the bone surface, thereby producing the protons required to continue bone resorption. In addition, they also reduce the activity of the osteoclasts, compromising the development of osteoclast progenitors, along with the recruitment and promotion of apoptosis of the osteoclasts. There also appears to be a beneficial effect on the osteoblasts [39].

Bisphosphonates can be administered orally (alendronate, risedronate, ibandronate) or intravenously (zoledronic acid at a dose of 5 mg every 12 months, and ibandronate in a dose of 3 mg every 3 months) [38, 40–43]. They avidly bind to bone minerals, especially to trabecular bone, with a high degree of specificity [44]. However, oral absorption is low (0.6–1.5 % of the administered dose). Approximately 40–60 % of the dose is distributed in the bone, the remainder being excreted unchanged in the urine without substantial metabolism [38].

Oral bisphosphonates should be taken once a week after fasting, (alendronate in a dose of 70 mg, and risendronate in a 150 mg dose), once a month (ibandronate in a dose of 70 mg or risendronate in a 150 mg dose), or on 2 consecutive days, once a month (risendronate in a dose of 75 mg). The patient must remain upright for at least 30 min after taking the drug in order to minimize gastroesophageal reflux and enhance absorption. Afterwards, food, medications, and other liquids should be avoided for at least 30–45 min [40].

Oral and intravenous bisphosphonates are contraindicated in patients who have had previous allergic reactions to any bisphosphonate, or creatinine clearance estimated at 35 ml/min or less, vitamin D deficiency (serum 25 hydroxy-vitamin D less than 30 ng/ml), osteomalacia or hypocalcemia [40].

Oral bisphosphonates are also contraindicated in patients with impaired swallowing, or esophageal disorders such as achalasia, esophageal varices, severe gastroesophageal reflux, or those who are unable to sit for at least 30 min after taking the medication [40].

An acute phase reaction (fever, myalgia, bone pain and weakness) occurs in 20 % of patients after an initial intravenous infusion of bisphosphonate and, in a very small number of patients, during oral therapy. Erosive esophagitis, ulceration, and bleeding have been associated with daily oral therapy using alendronate or risedronate, but seldom occur with the current regimes (not daily). Heartburn, chest pain, hoarseness, and irritation of the vocal cords can occur with weekly (alendronate or risedronate) or monthly therapy (ibandronate or risedronate) [40].

Osteonecrosis of the jaw is a rare but serious complication of long-term therapy that can appear spontaneously, or after dental surgery. Case reports suggest that atypical fractures of the femur (subtrochanteric and mid-diaphyseal portions) may also occur during prolonged therapy [40, 45].

There are no known interactions between bisphosphonates and other drugs. Evidence of treatment failure with patients adhering properly to a treatment regime indicates the need to change from orally administered bisphosphonate to intravenous zoledronic or another class of drugs, such as anabolic agents (e.g., teriparatide) [40].

Bisphosphonates suppress biochemical indices of bone resorption by around 50 % in a month, significantly reducing the incidence of vertebral, and non-vertebral fractures, including femoral fractures in patients with osteoporosis within a few months after the start of therapy [44].

BMD increases modestly by around 2–6 % during the first year of treatment. In the lumbar spine, it continues to increase slowly for several years, but in the femur, it reaches a plateau after about 2 years. Therapy preserves bone, but does not increase bone volume, or restore the bone structure [44].