Osteoporosis is a leading contributor of fractures worldwide, causing more than 8.9 million fractures annually.
Osteoporosis affects an estimated 200 million women worldwide (approximately 1/10th of women aged 60, 1/5th of women aged 70, 2/5ths of women aged 80, and 2/3rds of women aged 90). One in three women and one in five men over 50 will experience an osteoporotic fracture. Additionally, 61% of all osteoporotic fractures occur in women.
It has been predicted that the incidence of hip fracture is expected to increase by 310% in men and 240% in women by 2050. The economic toll of osteoporosis is expected to significantly increase. Indeed, it has been estimated that there is a 40% lifetime risk for fractures affecting the hip, forearm and vertebrae (similar to the risk for cardiovascular disease), with nearly 75% of these types of fractures occurring in patients aged 65 years age and above.
Osteoporosis has been shown to account for more days spent in the hospital than diabetes, heart attacks, or breast cancer. It is also a major cause of disability, which has been shown to be greater than that caused by cancer (except lung cancer) and comparable to or greater than disability from rheumatoid arthritis, asthma and high blood pressure related heart disease. The overall mortality within the first 12 months after a hip fracture is approximately 20%, being higher in men than women.
Men make up 20-25% of all hip fractures and have an estimated 30% lifetime risk of experiencing an osteoporotic fracture when over 50, similar to the lifetime risk of developing prostate cancer. Fragility fractures are the primary cause of hospitalisation and/or death for US adults ≥age 65 and above. Furthermore, 44% of nursing home admissions are due to fractures.
It is obvious that osteoporosis is extremely common, and this condition leads to disability, costs, and even death.
Bisphosphonates are a class of drugs that are used to prevent bone loss demineralisation (weakening or destruction). These have been used since the 1970s, but technological developments in recent years have continued to reduce the frequency of dosage and made other stronger forms of the drugs available.
Osteoporosis is caused by the cumulative effect of bone resorption in excess of bone formation.
Bisphosphonates inhibit bone resorption with relatively few side effects. As a result, they are widely used for the prevention and treatment of osteoporosis.
Bisphosphonates are also used in the management of hypercalcemia, Paget disease, and a number of malignancies, including multiple myeloma, breast cancer, and prostate cancer. These topics are all reviewed separately in the appropriate topic reviews.
The treatment of osteoporosis consists of lifestyle measures and pharmacologic therapy. Lifestyle measures include adequate calcium and vitamin D, exercise, smoking cessation, counselling on fall prevention, and avoidance of heavy alcohol use.
These measures should be adopted universally to reduce bone loss in postmenopausal women.
In addition to lifestyle measures, patients at high risk for fracture should receive pharmacologic therapy.
In the absence of specific contraindications, oral bisphosphonates are considered initial pharmacologic therapy for most postmenopausal women at high risk for fracture. Oral bisphosphonates are preferred as initial therapy because of their efficacy, favourable cost, and the availability of long-term safety data.
For patients with contraindications to oral bisphosphonates (eg, achalasia, oesophageal stricture, oesophageal varices, Barrett’s oesophagus), gastrointestinal (GI) intolerance to oral bisphosphonates, or an inability to follow the dosing requirements (e.g., stay upright for at least 30 minutes), we suggest an intravenous (IV) bisphosphonate formulation.
Oral bisphosphonates should not be used as initial therapy in patients with oesophageal disorders (e.g., achalasia, oesophageal stricture, oesophageal varices, Barrett’s oesophagus, etc) or with an inability to follow the dosing requirements (e.g., stay upright for at least 30 minutes). Oral bisphosphonates should also be avoided after certain types of bariatric surgery in which surgical anastomoses are present in the GI tract (e.g., Roux-en-Y gastric bypass); IV bisphosphonates are acceptable as long as vitamin D has been assessed and is in the normal range.
Oral and IV bisphosphonates should not be used routinely in patients with chronic kidney disease (CKD) and an estimated glomerular filtration rate (eGFR) <30-35 ml/min.
Before commencing bisphosphonate therapy, patients should be evaluated to detect potentially remediable causes of or other contributing factors to osteoporosis.
This evaluation includes assessment for hypocalcaemia, vitamin D deficiency, and renal impairment by measuring serum:
- 25-hydroxyvitamin D (25[OH]D)
For both oral and IV bisphosphonates, correction of hypocalcaemia and/or vitamin D deficiency is necessary prior to administration.
Bisphosphonates are poorly absorbed orally (less than 1% of the dose) and must be taken on an empty stomach for maximal absorption.
The following regimen is recommended to maximise absorption and minimise the risk of oesophageal adverse effects.
Bear in mind that bisphosphonates should:
- Not be given to patients with active upper GI disease
- Be discontinued in patients who develop any symptoms of oesophagitis
- Be taken alone on an empty stomach first thing in the morning with at least 240ml of water. After administration, the patient should not have food, drink, medications, or supplements for one hour.
The reason for taking a glass of water is to minimise the risk of the tablet getting stuck in the oesophagus.
The reason for taking the medication while fasting and waiting one half-hour until eating or drinking is that bioavailability may be seriously impaired by ingestion with liquids other than plain water, such as mineral water, coffee, or juice; by retained gastric contents, as with insufficient fasting time or gastroparesis; or by eating or drinking too soon afterwards.
Patients should remain upright (sitting or standing) for at least 30 minutes after administration to minimise the risk of reflux. Compliance is important for optimal fracture reduction.