July 2019, Volume XXXIII, No 4
Osteoporotic vertebral compression fractures
“The workouts have positively impacted the astronauts’ bones and muscles, and they are coming back in really good shape. But some are losing bone and muscle but not as much as we saw in the early days.”
—Scott Kelly, NASA Astronaut (Ret.), 520 days in space, the most cumulative time in space for an American.
steoporosis (OPO) is a disease characterized by low bone mineral density (BMD). The concomitant micro architectural deterioration leads to fragility and consequently increased fracture risk. Fragility fractures (FFs) result from either a fall from standing height or less or in the absence of trauma. The most common sites of FF are: femoral neck/hip, wrist, spine (thoracic and lumbar most common), humerus, pelvis, and forearm. The 10-year probability of FFs can be assessed using the Fracture Risk Assessment Tool (FRAX, www.sheffield.ac.uk/FRAX/), which stratifies risk according to: ethnicity, age, sex, weight, height, fracture history, family history of femoral neck/hip fracture, current smoking status, history of glucocorticoid use, history of rheumatoid arthritis, history of secondary OPO, history of alcohol consumption ≥3 beverages/day, and femoral neck/hip BMD.
OPO poses a Brobdingnagian public health problem, with approximately 16 percent of adults (5 percent men and 25 percent women) ≥65 years affected, according to the Centers for Disease Control and Prevention—an estimated 8 million Americans, according to U.S. census data. This is also a global issue affecting a calculated 8.5 percent of the word population ≥65 years (www.worldbank.org/data).
OPO incidence varies with race: Hispanics (25 percent), whites (16 percent), and African Americans (10 percent). Marriage or cohabitating appears to decrease the risk—perhaps due to lower levels of psychosocial stress—while occupation, employment status, and residence have limited associations. Income and education yield mixed and inconsistent associations.
Osteoporosis incidence varies with race.
In 2016, the mean impact of treating an FF in the U.S. was $10,300 per patient, with a cumulative cost to taxpayers of $17 billion. Some European Union countries have established fracture liaison services to ensure patients receive appropriate preventive care. Estimated cost savings with implementation of these programs is approximately $30,000 per 1,000 patients treated. Not only do FFs result in pain, functional disability, and decreased quality of life; they are associated with an increased risk of death within five years of diagnosis. Despite effective treatments to stabilize BMD and decrease FF risk, there is a lack of appropriate care. In the U.S., fewer than 20 percent of patients who sustain an FF receive therapy to decrease FF risk within a year of diagnosis, and <10 percent of elderly women with OPO receive therapy. There are multiple reasons for this. Media, in conjunction with product liability attorneys, have emphasized rare complications of bisphosphonate medication therapy—osteonecrosis of the jaw, atypical femoral neck/hip fractures, and atrial fibrillation—while ignoring patient and societal benefits. Physician surveys have indicated that providers fear complications of treatment more than the morbidity of OPO/FF.
Preventive care. World Health Organization (WHO) criteria for medical management of OPO/BMD are: history of femoral neck/hip or spine FF at ≥40 years, BMD T-score ≤−2.5, or BMD T-score −2.5 to −1.0 with an elevated FRAX ≥20 percent for non-femoral neck/hip major FF, and/or FRAX ≥3 percent for femoral neck/hip FF. U.S. guidelines for screening are: dual energy X-ray absorption (DXA) measurements of the femoral neck/hip and lumbar spine in women ≥65 years without risk factors or ≤65 years with risk factors and/or known FF. Routine screening of men is currently not supported by the medical literature; however, some authors advocate screening men ≥70 years without risk factors and ≤70 years with known risk factors or history of FF (www.uspreventiveservicestaskforce.org). Prospective study of women ≥65 years demonstrated that neither repeated DXA measurement nor the change in BMD after eight years was more predictive of subsequent FF risk than the BMD original measurement.
Providers should obtain a detailed patient medical history with emphasis on drug classes with known OPO association such as: androgen deprivation therapy, anticoagulants, anticonvulsants, aromatase inhibitors, calcineurin inhibitors, glucocorticoids, medroxyprogesterone, proton pump inhibitors, selective serotonin inhibitors, and thiazolidinediones. Comorbid conditions, such as diabetes, chronic obstructive pulmonary disease, gastrointestinal diseases of malabsorption, dementia, and rheumatoid arthritis, are also strongly associated with OPO. Alcohol, tobacco, and drug abuse should also be documented along with cessation counseling. Fall-risk assessment is important and can be obtained in consultation with physical therapy (PT). A PT program should strengthen antigravity muscles and promote postural retraining, helping prevent deformity and mitigating fall-risk. Physical exercise using progressive and safe-monitored activities has been demonstrated to preserve and increase BMD and to improve physical function.
Pharmacologic Management. Those patients meeting WHO criteria should be treated. Medication should be tailored to the individual patient, and an endocrinology consultation is strongly encouraged, especially if combination therapy is considered.
Bisphosphonate anti-resorptive agents are generally considered first-line therapy, having been shown to reduce the risk of hip and vertebral compression fractures (VCFs). Bisphosphonates are well studied, generally safe, and cost-effective. Before initiating therapy, patients should have a dental evaluation and complete any necessary invasive dental procedures. Zoledronic acid is the most potent bisphosphonate, published in the HORIZON study in 2007. The trial examined 7,765 patients randomly assigned to receive single treatment versus placebo infusion with one-year follow-up. Treatment resulted in a significant increase in BMDs of the spine and hip and significant decrease in FFs. A drug holiday may be considered in those patients who have been treated for five years with oral bisphosphonates or three years with IV bisphosphonate if no fractures have occurred, are considered low risk for FF, and whose T-score is greater than −2.5.
Denosumab is a monoclonal antibody that decreases bone turnover by inhibiting osteoclast differentiation. It is generally not a first-line medication but can be effective for patients with chronic renal disease. Hypocalcemia, increased risk of serious infection or skin infection, and rarely osteonecrosis of the jaw are the most common potential adverse effects. The FREEDOM trial randomized 7,868 women OPO patients to receive treatment or placebo every six months with 36 months of follow-up. There was a statistically significant increase in BMD of the hip and spine and a significant decrease in FFs. Optimal duration of therapy is unknown and BMD does decline with cessation.
Some European Union countries have established fracture liaison services.