July 2019, Volume XXXIII, No 4


Osteoporotic vertebral compression fractures

Evidence-based management

“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.

Medical Management

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.

Teriparatide, a recombinant form of parathyroid hormone, is a potent anabolic agent and is utilized in patients who have been intolerant or experienced further FFs on other treatments, or in those with severe OPO. It is typically used for two years and then followed by an anti-resorptive agent to maintain gains in BMD. It should not be used in persons with primary or secondary hyperparathyroidism, hypercalcemia, those with skeletal malignancies or metastasis, patients at increased risk for osteosarcoma or with unexplained elevations in alkaline phosphatase, or with a history of radiation. The pivotal trial published in 2001 enrolled 1,637 postmenopausal women randomized to receive either treatment with 1 of 2 doses (20 μg/d 544 patients or 40 μg/d 552 patients) compared with 544 placebo-receiving patients. The trial demonstrated significant increases in BMD of the hip and spine with a significant reduction in FFs.

Hormone replacement therapy and raloxifene are anti-resorptive therapies. Estrogen is no longer considered first-line treatment due to the well-known risks of breast and endometrial cancers, thromboembolic disease, and stroke. The MORE study (7,705 women, 31–80 years, placebo controlled) tested two doses of raloxifene, a selective estrogen receptor modulator, versus placebo and demonstrated that treatment increased hip and spine BMD and decreased risk of FFs.

Calcitonin is an anti-resorptive peptide that reduces osteoclast function. It has been used for many years and has been associated with decreased pain of VCF. Recently, the European Medicines Agency (www.ema.europa.eu) concluded that “the benefits of calcitonin containing medicines do not outweigh their risks in the treatment of OPO and they should no longer be used for this condition.”

Vertebral compression fracture management

Pain management is the cornerstone of VCF treatment. The first-line use of opioids in the setting of severe acute pain is reasonable, but caution must be exercised. Significant problems may occur when prescribing these agents to elderly patients: altered mental status, increased fall risk, and other medical complications. Opioids should be dose- and duration-limited with a planned early transition to either other agents or methods of pain control.

Bracing has traditionally been prescribed for pain and prevention of deformity. Clinical trials have demonstrated mixed results with regard to pain management and failed to protect patients from progressive kyphosis. Percutaneous procedures that inject polymethylmethacrylate (PMMA) bone cement  into a VCF, such as vertebroplasty (VP) and/or kyphoplasty (KP), are postulated to provide structural support and pain control. The two techniques are practically the same and may be considered equivalent. Industry-sponsored KP studies used to obtain FDA clearance were designed as non-inferiority trials and were not designed nor sufficiently powered to demonstrate superiority of KP over VP.

Buchbinder et al. reported the first randomized clinical trial of VP versus sham procedure in the New England Journal of Medicine in 2009. A total of 78 patients were randomized to either VP (35/38) or sham procedure (36/40) using an intention-to-treat analysis. The results failed to show a clinical advantage to VP. A more recent meta-analysis of VP using two placebo controlled randomized controlled studies was published by the Cochrane Collaboration in 2015. Key conclusions were that VP did not differ from placebo for pain and quality of life at one month and no statistically significant difference with regards to patient judgment of success.

VP and KP also have known low incidence perioperative risks: PMMA embolism, spinal cord/spinal nerve root compression, osteomyelitis, and adjacent segment VCF. Routine VP/KP of VCFs as first-line therapy is therefore not indicated and should be reserved for patients failing conservative management or with spine structure, alignment, and/or stability factors requiring a more aggressive treatment. In those cases, the quality of PMMA fill and preservation of height and alignment are important.

Spinal instrumentation may be used for progressive or severe deformity requiring correction. Procedures have both risks and limitations; the surgery may be extensive, especially in the setting of poor BMD and/or severe deformity with adverse effects that include: significant blood loss potentially requiring transfusion, the associated risk of receiving blood products and perioperative complications such as myocardial infarction, respiratory failure, acute renal injury, and multi-organ system failure. The chance of an adverse event is elevated in elderly patients, and a careful preoperative risk assessment with physiological optimization must be done prior to consideration. In some patients, risks may be mitigated with the use of percutaneous instrumentation with or without concurrent VP/KP. Other delayed risks to consider are: generating a proximal kyphotic deformity at the segment just cranial to the last instrumented level (which is elevated in patients with OPO), instrumentation failure, and non-healing bone (pseudarthrosis). These surgeries also have permanent effects on spinal flexibility and mobility that may increase fall risk and require a long convalescence. In the OPO patients, it is important to remember that postoperative bone growth and remodeling, which is necessary for fusion, may be hindered by the underlying diagnosis as well as comorbidities such as: smoking, alcohol consumption, malnutrition, and other comorbidities that contributed to the development of OPO.


As a large population of baby boomers begins to reach ≥65 years, the prevalence of OPO and associated comorbid conditions along with FFs and VCFs will increase. Utilization of evidence-based therapies will help optimize patient outcomes and contain societal costs. In general, medical management of OPO and VCFs is preferred. Interventions such as VP/KP, bracing, and spinal fusion with instrumentation are options in those patients who fail to respond or are at risk of spinal instability and/or deformity.

Charles R. Watts, MD, PhD, is a staff neurosurgeon with Health Partners/Park Nicollet and practices at Methodist Hospital, St. Louis Park. He is board-certified in neurosurgery, surgery critical care, and neurocritical care.

Thomas Sorenson, BS, is a medical student at the University of Minnesota’s College of Medicine in Minneapolis.

Jane M. Korducki, MD, is the chair of the Department of Endocrinology, Mayo Clinic Health System–La Crosse and practices in La Crosse, WI. 

This article is a condensed version of “Comprehensive Management of Osteoporotic Thoracic and Lumbar Vertebral Compression Fractures,” published in Contemporary Neurosurgery, Vol. 40, No. 16, 2018, DOI: 10.1097/01.CNE.0000547765.47045.88.


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Jane M. Korducki, MD, is the chair of the Department of Endocrinology, Mayo Clinic Health System–La Crosse and practices in La Crosse, WI.