Osteoporotic thoracolumbar vertebral compression fractures: Clinical manifestations and treatment

INTRODUCTION — Osteoporotic fractures (fragility fractures, low-trauma fractures) are those occurring from a fall from a standing height or less, without major trauma such as a motor vehicle accident. Vertebral compression fractures are the most common type of osteoporotic fracture [1]. They often occur at the midthoracic (T7-T8) spine and the thoracolumbar junction (T12-L1). Fractures may result in significant back pain, limited physical functioning and activities of daily living, and can lead to loss of independence, depression, and chronic pain. Osteoporotic fracture is an important risk factor for subsequent fracture.

This topic will review the clinical manifestations, diagnosis, and management of acute osteoporotic vertebral compression fractures. The diagnosis and treatment of osteoporosis are reviewed separately. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women" and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men" and "Overview of the management of low bone mass and osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)

CLINICAL MANIFESTATIONS

Symptoms and signs — Acute vertebral body compression fractures are associated with pain. The pain may be tolerable and resolve without medical intervention (but the patient can often recall the episode of pain when a fracture is incidentally found on other imaging), or the pain may be incapacitating, requiring hospital admission and parenteral opioids. In contrast, osteoporotic vertebral compression that occurs slowly over time is often asymptomatic. Old or healed fractures may be an incidental finding on radiographs of the chest or abdomen. In other patients, the presence of vertebral fractures may become apparent because of height loss or kyphosis [2]. (See 'Height loss' below and 'Kyphosis' below.)

In patients who have acute symptomatic vertebral body fracture, there is often no history of preceding trauma. The typical patient presents with acute back pain after sudden bending, coughing, or lifting. Occasionally, minor trauma, such as going over speed bumps, may precipitate a fracture [3]. The pain is usually well localized to the midline spine but often refers in a unilateral or bilateral pattern into the flank, anterior abdomen, or the posterior superior iliac spine. By contrast, radiation of pain into the legs, as may be seen with a herniated disc, is rare with compression fractures but may herald spinal cord or nerve root compression from retropulsed bone fragments.

The pain from a vertebral compression fracture is variable in quality and may be sharp or dull. Sitting, spine extension, Valsalva maneuver, and movement often aggravate the pain and may be accompanied by muscle spasms. Sleep may be disturbed by pain. On physical examination, the patient may experience pain upon palpation and percussion of the corresponding spinous process and paravertebral structures.

Acute episodes of pain following a vertebral body fracture usually resolve after four to six weeks, but pain may persist for longer periods (many months), indicating an unhealed or slowly healing fracture. Severe back pain that presents after a normal period of healing may indicate additional fractures or another diagnosis.

Functional impairment from vertebral fracture is often comparable with that related to hip fracture, including difficulty bending, lifting, reaching, walking down stairs, or cooking [4,5]. Approximately 75 percent of patients who present with a symptomatic vertebral fracture complain of chronic pain [6,7].

Height loss — Height loss from osteoporosis is typically asymptomatic and gradual. In addition to osteoporotic compression fractures, height loss can be caused by disc desiccation and resultant disc space narrowing or scoliosis. In one study, historical height loss of >6 cm had a specificity and sensitivity of 94 and 30 percent, respectively, for detection of vertebral fracture [8].

Kyphosis — Kyphosis ("dowager hump") may be an indicator of multiple vertebral compression fractures, especially wedge fractures, although kyphosis may occur independently of vertebral abnormalities (figure 1). Each complete compression fracture causes approximately 1 cm or more loss in height; loss of more than 4 cm in height is associated with 15 degrees of kyphosis. Practically, however, there are no simple clinical measures of kyphosis, and measures of height may be inconsistent due to variabilities in measurement technique and posture. Some potentially useful clinical measurements include the distance from the occiput to the wall (normally 0 cm) and the size of the gap between the costal margin and the iliac crest (normally three fingerbreadths) [9]. Measuring kyphosis is discussed in more detail elsewhere. (See "Hyperkyphosis in older persons".)

Patients with kyphosis may complain of a protuberant abdomen, that their clothes do not fit, or that they no longer have a waist. They may also complain of early satiety. These symptoms reflect the compression of the abdominal contents as a result of kyphosis.

Patients with severe thoracic kyphosis often complain of mechanical neck pain or headache since they must forcefully extend their necks in order to look forward. They often have cervical facet disease and degenerative disc disease due to the hyperextension of the cervical spine in order to remain upright. Restrictive pulmonary disease may become apparent with severe kyphosis [10].

A costo-iliac impingement syndrome can develop in patients with kyphosis following multiple vertebral fractures, wherein the most inferior rib impinges against the iliac crest due to a reduction in the normal distance between the bottom of the rib cage and the top of the iliac crests [11,12]. This causes pain in the region of the 12^th thoracic vertebra that radiates to the posterior trunk. Patients may also complain of hip pain and, when pressed for details, can pinpoint the sensation to the superior iliac crest.

Risk of subsequent fracture — A history of an osteoporotic fracture is a risk factor for subsequent fractures. Approximately 19 percent of patients who have a vertebral compression fracture will have another fracture in the next year [13]. In one analysis of the literature, women with preexisting vertebral fractures had approximately four times greater risk of subsequent vertebral fractures than women without prior fractures [14]. The presence of vertebral fractures also predicts future nonvertebral fractures, particularly hip fracture, and this risk increases with the number and severity of prior fractures [15]. (See "Osteoporotic fracture risk assessment", section on 'Personal history of fracture as an adult'.)

DIAGNOSIS — Patients with a suspected acute vertebral body compression fracture should be evaluated with plain radiographs of the thoracolumbar spine to confirm the diagnosis.

Imaging abnormalities — Osteoporosis may lead to several types of vertebral abnormalities, including wedge fractures, biconcave or "codfish" deformities, and compression fractures (figure 2). Radiographic characteristics of compression fractures include anterior wedging of one or more vertebrae with vertebral collapse, vertebral endplate irregularity, and general demineralization (image 1). Posterior wedging is uncommon and may indicate an underlying destructive lesion. The severity of vertebral fractures may be radiographically staged as follows [16]:

●Grade 1 – 20 to 25 percent height deformity

●Grade 2 – 25 to 40 percent height deformity

●Grade 3 – >40 percent height deformity

Differential diagnosis — Compression fracture may be the first symptom of osteoporosis. It is important to appreciate certain clues that suggest that vertebral fractures might be due to causes other than uncomplicated osteoporosis:

●Fracture occurring in a person who is not older

●A solitary vertebral fracture in vertebrae higher than T4 is unusual, unless there are also multiple vertebral fractures at lower levels [17]

In these settings, other causes of low bone mass (eg, osteomalacia, hyperparathyroidism, granulomatous diseases, hematologic diseases, infections, or metastatic cancer) should be excluded. (See 'Evaluation' below and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Evaluation'.)

Juvenile kyphosis (Scheuermann disease) and adult or adolescent kyphosis also should be differentiated from compression fractures. The vertebral abnormalities of Scheuermann disease include endplate irregularities and wedging of the vertebral body without low bone density. (See "Hyperkyphosis in older persons" and "Back pain in children and adolescents: Causes", section on 'Scheuermann (juvenile) kyphosis'.)

EVALUATION

●Neurologic examination – The patient should be assessed for neurologic findings (dermatomal sensory deficits, focal weakness, upper motor neuron signs like clonus). Neurologic abnormalities may indicate retropulsed bone fragments in the spinal canal or foraminae that may demand surgical intervention. In such patients, an urgent magnetic resonance imaging (MRI) or computed tomography (CT) scan should be obtained with prompt consultation with a spine surgeon.

●Laboratory testing – Laboratory evaluation may also be indicated to diagnose secondary causes of osteoporosis such as renal or liver disease, hyperthyroidism, hyperparathyroidism, Cushing syndrome or subclinical hypercortisolism, early menopause, hypogonadism, celiac disease and other forms of malabsorption, idiopathic hypercalciuria, or connective tissue disorders (table 1).

•For the initial evaluation, we typically measure a complete blood count (CBC), biochemistry profile (calcium, phosphorous, albumin, total protein, creatinine, liver enzymes including alkaline phosphatase, electrolytes), 25-hydroxyvitamin D, and, in men, a serum testosterone level. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in men", section on 'Evaluation' and "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Initial evaluation'.)

Patients who have abnormalities on the initial laboratory testing or who have suspicious findings on history and physical examination may also require additional laboratory tests. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'Additional evaluation'.)

•Patients in whom malignancy is suspected due to weight loss or other clinical symptoms should have a CBC, serum alkaline phosphatase, serum and urine protein electrophoresis, and serum erythrocyte sedimentation rate or C-reactive protein. Radionucleotide bone scan can be performed to evaluate for the presence of metastatic (osteoblastic) bone lesions.

•Any febrile patient in whom infection is suspected should have a CBC, C-reactive protein, and blood cultures to evaluate for infection.

●Additional imaging

•An MRI or CT scan may also be considered when further diagnostic information is indicated (by the results of a plain radiograph or laboratory testing), though most patients will not need these imaging studies. MRI and CT are helpful to assess for retropulsion (axial images) when determining potential instability of a wedge fracture [18]. MRI is used to date the acuity of the fracture when such information is important (eg, determining whether a fracture is a source of recent-onset back pain), and, additionally, may provide information on whether there is an underlying malignancy [19]. If patient cannot get MRI (pacemaker, automatic implantable cardioverter-defibrillator [AICD], etc) then bone scan can assess the metabolic activity/age of the fracture.

•A dual-energy x-ray absorptiometry (DXA) bone density study, performed on a nonurgent basis, is preferred for quantitative assessment of bone density and assessment of future fracture risk.

After a diagnosis of osteoporosis has been made, a consultation with a clinician who has expertise in the management of osteoporosis is often helpful for providing osteoporosis treatment recommendations. (See 'Treatment for osteoporosis' below.)

MANAGEMENT

Our approach

Overview — The approach outlined below is based upon clinical experience and limited evidence from observational studies and randomized trials.

The initial management of osteoporotic vertebral compression fractures should include pain control and activity modification. Oral analgesics (eg, acetaminophen, ibuprofen, naproxen) with or without intranasal calcitonin are first-line therapy for the relief of acute pain (see 'Oral analgesics' below). Mild opioids combined with acetaminophen or mixed mechanism drugs (eg, tramadol, tapentadol), centrally acting analgesics whose mode of action is based both on mu-opioid receptor binding and monoamine (serotonin and norepinephrine) reuptake blockade, are options for inadequate analgesia after one to two weeks of initial therapy, or for severe pain.

The indications for and timing of vertebral augmentation procedures are controversial. Most patients with vertebral compression fractures can be treated successfully with conservative management [20]. However, vertebral augmentation may be beneficial in select patient groups (eg, incapacitating pain and in those who are not improving with conservative medical management). (See 'Severe pain' below and 'Selection of patients' below.)

Patients should resume physical activity as quickly as possible. Complete bedrest is not recommended, as inactivity may result in further bone loss and deconditioning. Physical therapy is recommended for gait and core strengthening when the patient can tolerate this level of activity [21]. Patient education is important. The patient should be informed that fractures may take up to three months to heal and that pain should diminish gradually with a commensurate improvement in activity tolerance. Lying supine with the hips and legs flexed (the 90/90 rest position) may be helpful in reducing pain (picture 1).

Long-term management should include medications to improve low bone density. For example, medications such as bisphosphonates or denosumab, preferably after a course of anabolic treatment (eg, teriparatide), lead to increased bone mass and a reduction in the rate of new fractures. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)

If present, underlying diseases (eg, osteomalacia, hyperparathyroidism, granulomatous diseases, hematologic diseases, infections, metastatic cancer) require further management.

Mild to moderate pain — Patients with mild to moderate pain can be treated initially with nonopioid oral analgesics (acetaminophen, ibuprofen, or naproxen). We initiate intranasal calcitonin early in the course of therapy (eg, at the same time as nonopioid oral analgesics). Calcitonin has been shown to hasten the relief of pain from osteoporotic vertebral fracture. Opioids are an option for when the patient reports inadequate analgesia after one to two weeks of initial pain medications. If opioids are indicated, immediate-release formulations should be used at the lowest effective dose. (See 'Oral analgesics' below and 'Calcitonin' below.)

Severe pain — Patients with severe pain from an acute (0 to 4 weeks) vertebral body fracture typically require opioids at the outset. If the pain is incapacitating, hospital admission and parenteral analgesia for pain management may be necessary. (See "Use of opioids for postoperative pain control" and "Approach to the management of acute pain in adults".)

Parenteral opioids are converted to oral formulation during the inpatient stay (typically three to seven days), and the clinician assesses the clinical efficacy of this transition. Intolerable side effects of these medications, particularly constipation, sedation, and delirium, are seen early after administration. Older adult and deconditioned patients and those with multiple comorbidities are more susceptible to the cognitive side effects of parenteral opioids. The rate of opioid tapering should be assessed on a case-by-case basis, based on the patient's side-effect profile, level of function, and subjective reports of persistent ongoing pain. For patients with incapacitating pain from acute and subacute vertebral compression fractures, who are unable to transition from parenteral to oral opioids within seven days of admission or have intolerable sedation, constipation, or delirium from this therapy, we prefer vertebral augmentation during the initial hospitalization to continued medical management. (See 'Selection of patients' below.)

The majority of hospitalized patients with severe pain, however, are able to discontinue parenteral analgesia, report adequate pain control with oral analgesics (typically opioids), and are discharged from the hospital. Many will have slow improvement in pain, will be able to taper and discontinue opioids, and will begin physical therapy.

Persistent pain — Management options for patients with persistent pain (greater than six weeks of medical management) include continued medical management or vertebral augmentation. We suggest continued medical management for patients who have noticed some improvement in pain and who are able to tolerate, maintain, or taper opioids and begin a physical therapy program. For those who are not satisfied with the level of symptomatic relief (eg, even with higher doses of opioids), are unable to perform the activities of daily living, or are not tolerating opioids (constipation, confusion, urinary retention), we prefer vertebral augmentation to continued medical management. It is important to note that in some patients with persistent pain, the degree of vertebral compression may progress with time to such an extent that vertebral augmentation may be difficult to perform successfully. In such cases, continued medical management is the only option.

Chronic pain — Patients with chronic pain (three to six months post fracture) require further evaluation to determine if the fracture remains metabolically active (as evidenced by the presence of bone marrow edema) or if additional fractures or other pain generators may have developed. We perform a physical examination and MRI of the affected spine region. Tenderness to palpation/percussion at the level of the fracture and MRI findings of bone marrow edema are consistent with a nonhealing or slowly healing fracture. It may be helpful to identify the painful spinal level using fluoroscopy. Inpatients with nonhealing or slowly healing fracture, treatment options include continued medical management or vertebral augmentation [22]. Patients should be informed that there are few data evaluating vertebral augmentation in patients with chronic fractures and that pain may not improve after the procedure. (See 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)' below.)

For patients without findings of pain provocation on physical examination of the affected spine region and the absence of bone marrow edema on MRI (indicating a healed fracture), there is no role for vertebral augmentation. The patient should be evaluated for alternative causes of the pain. (See "Evaluation of low back pain in adults".)

Pharmacologic therapy

Oral analgesics — Oral analgesics are the first-line therapy for the relief of acute pain due to vertebral compression fractures. Acetaminophen (650 mg four times daily or 1 g three times daily), naproxen (220 to 500 mg twice daily), or ibuprofen (400 to 600 mg four times daily) is commonly used for mild to moderate pain, along with intranasal calcitonin (see 'Calcitonin' below). If pain does not improve with this initial therapy, oral opioids are alternative treatment options. Oral opioids are also an initial treatment option for patients who present with acute moderate-to-severe pain.

When opioids are required to control pain from vertebral compression fractures, we typically initiate treatment with an immediate-release opioid, a mu agonist (eg, tramadol, tapentadol), or a mixed agonist/antagonist like buprenorphine. An immediate-release opioid can be combined with low-dose acetaminophen (eg, hydrocodone 5 or 10 mg combined with acetaminophen 325 mg or, if ineffective or not tolerated [nausea, pruritus], oxycodone 5 mg with acetaminophen 325 mg). (See "Management of acute pain in opioid naïve adults in the ambulatory setting", section on 'Opioids'.)

Tramadol and tapentadol are centrally acting analgesics whose mode of action is based both on mu-opioid receptor binding and monoamine (serotonin and norepinephrine) reuptake blockade. They are considered mild analgesics. They both have serotonin-reuptake inhibition, so caution must be taken when patients are on other serotonin-reuptake inhibitors as serotonin syndrome could occur at higher doses. (See "Serotonin syndrome (serotonin toxicity)".)

Side effects of opioids include constipation, sedation, nausea, and pruritus. A laxative should be given to prevent straining at defecation as Valsalva maneuvers can acutely worsen pain symptoms and can cause further fractures. Opioid preparations and adverse effects are reviewed separately. (See "Pharmacologic management of chronic non-cancer pain in adults", section on 'Opioids'.)

The adverse effects of nonsteroidal antiinflammatory drugs (NSAIDs) are inhibition of platelets (except for cyclooxygenase-2 [COX-2] selective inhibitors) with potential promotion of bleeding, gastrointestinal insult, renal insult, and adverse cardiovascular effects. In studies in rodents, both nonselective and COX-2-selective NSAIDs can interfere with normal fracture healing, an effect that appears to be mediated by the inhibition of COX-2. However, a causal relationship has not been proven, and the effect of these drugs on fracture healing in humans is uncertain [23]. We would not avoid the use of these agents in patients with vertebral fractures. (See "Nonselective NSAIDs: Overview of adverse effects", section on 'Possible effect on fracture healing' and "Overview of COX-2 selective NSAIDs".)

The risk of NSAIDs needs to be considered carefully in older adults, especially older adult individuals with multiple comorbidities. In patients with cardiovascular disease, NSAIDs should be used in the lowest effective dose, for the shortest duration necessary. Cardiovascular and other adverse effects of NSAIDS are reviewed separately. (See "NSAIDs: Adverse cardiovascular effects" and "Nonselective NSAIDs: Overview of adverse effects".)

Calcitonin — For patients with mild to moderate pain, we initiate intranasal calcitonin early in the course of therapy (eg, with oral nonopioid analgesics). Calcitonin is not effective immediately [24]; therefore, initiating it with acetaminophen, ibuprofen, or naproxen allows the oral analgesics to provide some pain relief until the calcitonin becomes effective. It is generally continued for a two- to four-week course. In small randomized trials, calcitonin hastened the relief of pain from vertebral fractures, and it can be a useful adjunct to traditional analgesics in the acute setting (figure 3) [25-27]. Nasal calcitonin, 200 units (one spray) once daily alternating nostrils, may be more effective than the intramuscular preparation (figure 4). (See "Calcitonin in the prevention and treatment of osteoporosis", section on 'Bone pain'.)

Calcitonin is not a first-line agent for the treatment of osteoporosis, because it causes the least increase in bone mineral density (BMD) of any agent currently used and has been shown to reduce vertebral fracture risk only in one of three trials. After a two- to four-week course, the patient should be started on a more effective osteoporosis treatment regimen. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)

Drugs not routinely recommended

Bisphosphonates — We do not use oral or intravenous bisphosphonates for the management of acute pain from a fracture. Although in one small trial, intravenous pamidronate provided pain relief in patients with acute painful osteoporotic vertebral compression fracture [28], in another trial, intravenous pamidronate was not more effective than calcitonin for pain reduction in those with vertebral fractures [29]. However, bisphosphonates are a treatment option for the long-term management of osteoporosis. (See "Bisphosphonate therapy for the treatment of osteoporosis".)

Parathyroid hormone — PTH (1-34) reduces the severity and incidence of new spine fractures and has been shown to reduce new or worsening back pain in some clinical trials. While PTH is a good treatment option for patients with severe osteoporosis and vertebral compression fracture, there are insufficient data to recommend its use for pain control or fracture healing. (See "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Back pain' and "Parathyroid hormone/parathyroid hormone-related protein analog therapy for osteoporosis", section on 'Fracture healing'.)

Muscle relaxants — There are no clinical trials evaluating the efficacy of non-benzodiazepine skeletal muscle relaxants (eg, cyclobenzaprine, methocarbamol) for the relief of pain in patients with osteoporotic vertebral compression fractures. Although these medications have been shown to be modestly more effective than placebo for short-term relief of nonspecific, acute low back pain, they have significant adverse effects in older adults, and we suggest not using them. (See "Treatment of acute low back pain", section on 'Combination with muscle relaxants'.)

Vertebral augmentation procedures (vertebroplasty and kyphoplasty) — The trials evaluating the use of vertebral augmentation procedures are of variable quality, and therefore, the indications for and timing of these procedures for the treatment of osteoporotic compression fractures are controversial. (See 'Selection of patients' below and 'Efficacy of vertebral augmentation' below.)

Vertebroplasty and kyphoplasty involve the percutaneous injection of bone cement under image guidance into a fractured vertebra. Specific to kyphoplasty, inflatable bone tamps are placed into the fractured vertebral body to create a low pressure cavity in which bone cement is placed to reduce the fracture and, in theory, to improve kyphotic deformity [30]. Vertebral augmentation procedures are usually performed in an outpatient setting with sedation or general anesthesia; the optimal timing of the procedure related to fracture acuity is unclear [31,32]. The potential short-term benefit for both procedures is improvement in pain, whereas potential long-term benefits include prevention of recurrent pain at the treated level(s), avoidance of prolonged medication use (eg, opioids), limitation or reversal of height loss and spinal deformity, and improved functional capability.

Vertebroplasty or kyphoplasty for the treatment of malignancy-associated vertebral compression fractures is reviewed elsewhere. (See "Multiple myeloma: Overview of management", section on 'Skeletal lesions and bone health' and "Rehabilitative and integrative therapies for pain in patients with cancer".)

Selection of patients — Patient selection is a critical factor for both the decision to perform vertebral augmentation and the selection of the type of procedure.

●For patients with mild to moderate pain that is responding to medical management, vertebral augmentation is not indicated, because placebo (sham) controlled trials show no benefit compared with controls [33].

●For patients with incapacitating pain who are unable to taper parenteral opioids and for those who are not improving with or are intolerant of oral opioids (urinary retention, constipation, confusion), some clinicians, including the authors of this topic, suggest vertebral augmentation, while others prefer continuing medical management. Those against vertebral augmentation point to the best quality evidence that suggests no benefit [33], while those suggesting vertebral augmentation point to the absence of generalizable trial conclusions for patients who are not improving or are intolerant of usual therapy [34].

In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends vertebroplasty and kyphoplasty as possible treatment options for patients with osteoporotic spinal compression fractures who have severe, ongoing pain despite treatment for pain and in whom the pain is confirmed to emanate from a known fracture [35]. The American Society for Bone and Mineral Research (ASBMR) suggests against vertebral augmentation for patients with acute painful osteoporotic vertebral fractures [36].

There are insufficient data to firmly establish patient subgroups that would most likely benefit from vertebral augmentation. (See 'Efficacy of vertebral augmentation' below.)

Selection of procedure — While vertebroplasty and kyphoplasty appear to perform similarly, kyphoplasty is performed more frequently than vertebroplasty [37]. Vertebroplasty is performed when there is little to no compression of the vertebral body, but MRI shows bone marrow edema consistent with fracture. Vertebroplasty takes less time to perform, does not rely on the performance of a balloon system, and is less expensive. Kyphoplasty relies on the use of a balloon tamponade system that can have technical difficulties, but it may partially restore vertebral height. Systematic reviews and meta-analyses of randomized trials comparing the procedures have not shown significant differences in short- or long-term pain scores, short- or long-term disability scores, or adjacent level fracture rates [33,38,39].

Efficacy of vertebral augmentation

Overall efficacy — Evidence supporting the use of these procedures to reduce pain and disability is mixed, due to variability in study design and quality [40]. Most of the systematic reviews and meta-analyses have evaluated vertebroplasty, rather than kyphoplasty, as high-quality evidence from placebo-controlled kyphoplasty trials is lacking.

●Pain and disability – In the majority of systematic reviews, sham (placebo)-controlled trials do not show a clinically important benefit of vertebroplasty, whereas trials comparing vertebroplasty with usual care generally favor vertebroplasty with regard to improvement in pain and disability [33,41-43]. As an example, in one analysis of 21 randomized trials (five compared vertebroplasty with a sham procedure, eight compared vertebroplasty with usual care, seven compared vertebroplasty with kyphoplasty, and one compared vertebroplasty with facet joint glucocorticoid injection), there was no difference between vertebroplasty and sham procedure with respect to pain (pain score at one month on a 0 to 10 point scale, 4.4 and 5 for vertebroplasty and placebo, respectively), disability, and disease-specific or overall quality of life [33]. In the trials comparing vertebroplasty with usual care, there was a significant reduction in pain and disability favoring vertebral augmentation at all time points up to 12 months (eg, standardized mean difference in pain score at one month -2.06, 95% CI -3.35 to -0.76). The trials that were not sham controlled may have overestimated benefit due to lack of participant and study personnel blinding. Overall, the meta-analyses are limited by significant heterogeneity of the study results, suggesting that additional trials, with uniform criteria for patient enrollment and assessment of pain relief, are needed in order to better characterize the potential benefits of these procedures. Some of the individual trials are reviewed below. (See 'Vertebroplasty' below and 'Kyphoplasty' below.)

●Mortality – There are few high-quality studies that address mortality. In a meta-analysis of observational studies, operative management with vertebroplasty or kyphoplasty was associated with a lower mortality than nonoperative management [44]. In these observational studies, propensity matching may not have adjusted for selection bias, ie, providers selecting patients for vertebral augmentation who were less likely to have complications. Similar to the trials comparing vertebral augmentation with usual care, these results may overestimate the benefits of operative management.

Vertebroplasty — In unblinded, randomized trials comparing vertebroplasty with pain management, there was greater improvement in pain immediately after vertebroplasty (one day) but not at two weeks [45], three months [46], or 12 months [47,48]. In one trial, the improvement in pain after vertebroplasty was significant at one day, one month, and one year [49]. However, the trial was not blinded, and the observed results may be attributed, in part, to a placebo response and to biased patient-reported outcomes (patients who received vertebroplasty exaggerated reported pain relief because of prior expectations by patient and/or investigator) [50]. In addition, more than half of the patients who initially qualified for the study had spontaneous reduction or resolution of pain (mean pain score <5) during screening and therefore were not eligible for inclusion in the study.

Two sham-controlled trials of vertebroplasty in patients with osteoporotic compression fractures did not show a significant benefit in reducing pain [51,52] but were criticized for methodological flaws in study design [53]. Subsequent sham-controlled trials reported conflicting results, with one showing significant improvement in pain scores with vertebroplasty [54] and the other showing no greater pain relief than a sham procedure [55].

●In the first trial, vertebroplasty was compared with a simulated procedure without cement in 131 patients who had one to three painful osteoporotic vertebral compression fractures, pain scores greater than or equal to 3 (0 to 10 scale), and less than 12 months of back pain presumably from a vertebral fracture [52]. The primary outcomes were improvements in function as measured by the modified Roland-Morris Disability Questionnaire and pain intensity (on a scale of 0 to 10) during the previous 24 hours. Outcomes were reported at 3, 14, and 30 days.

The improvement in disability and pain scores was similar in both groups at all time points (three days, two weeks, one month [difference at one month, 0.7, 95% CI -1.3 to 2.8 and 0.7, 95% CI -0.3 to 1.7 for disability and pain scores, respectively]). In both groups, the greatest improvement occurred within three days of the procedure and was maintained at one month. Problems with the study design and analysis included modification of the study sample size due to difficulty in recruitment, failure to confirm bone marrow edema at the sites of fractures in all patients, and high rates of crossover in the control to vertebroplasty arm (43 versus 12 percent from vertebroplasty to control).

●In the second sham-controlled, multicenter trial, 78 patients were randomly assigned to either vertebroplasty or a simulated sham procedure over a 4.5-year period [51]. The study was terminated early despite not attaining the proposed sample size in the original power analysis. Inclusion criteria for this study included the presence of back pain for less than 12 months, one or two vertebral fractures, and an MRI confirming a fracture line, bone marrow edema, or both.

No differences in patient outcomes were identified between the vertebroplasty and the sham-control group (difference in pain scores at three months 0.6, 95% CI -0.7 to 1.8). The inclusion criteria in this trial were strongly criticized because the study population was believed not to represent definitively the acute or subacute fracture population, in whom vertebroplasty may be most beneficial [53]. However, the median duration of back pain was nine weeks, and only two participants in each group had symptoms for longer than six months. In addition, all participants were required to have had bone edema on MRI in the affected vertebrae.

●In the third sham-controlled trial, which was sponsored by the device manufacturer, 120 patients with acute vertebral fracture (less than six weeks' duration) and back pain (pain score ≥7 out of 10) were randomly assigned to vertebroplasty or simulated vertebroplasty (subcutaneous lidocaine, but not periosteal numbing) [54]. At 14 days, a greater proportion of patients in the vertebroplasty group had a pain score of <4 out of 10 (44 versus 21 percent). Similar findings were noted at one, three, and six months. The mean reduction in the Roland-Morris Disability scores at one, three, and six months after treatment was greater in the vertebroplasty group.

●In the fourth sham-controlled trial, 180 individuals with one to three acute, painful osteoporotic vertebral compression fractures (less than six to nine weeks' duration) were randomly assigned to vertebroplasty or to a sham procedure [55]. Both groups received local subcutaneous lidocaine and bupivacaine in each pedicle, but only the vertebroplasty group received cementation. Compared with baseline, the mean reduction in pain scores was significant in both groups at all time points. However, the change in pain score did not differ significantly between groups at any time point (1, 3, 6, and 12 months). There was no difference at any time point between the two groups in use of analgesics, changes in quality of life, or changes in disability questionnaire (Roland-Morris) scores.

The discrepant results among the trials raise the question as to what is the optimum control procedure for vertebroplasty. In the three trials that did not show a reduction in pain with vertebroplasty, the sham (simulated) procedure included the same periosteal as well as subcutaneous anesthetic as used for the vertebroplasty procedure, but in the third trial, the sham procedure consisted of only the subcutaneous anesthetic. It is uncertain if this difference would account for differences in pain at 14 days as the duration of the local anesthetic effect would be approximately one to eight hours.

Kyphoplasty — Kyphoplasty is procedurally distinct from vertebroplasty (see 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)' above). In observational studies, kyphoplasty reduced pain and disability in patients with osteoporotic vertebral compression fractures [31,56-59]. Data from randomized trials are limited, and there are no sham-controlled trials [38]. In the largest trial to date, 300 patients with one to three acute (mean six weeks old) vertebral fractures were randomly assigned to kyphoplasty versus nonsurgical care (not a sham procedure as in the above vertebroplasty trials) [60]. After one month, patients assigned to kyphoplasty had greater improvement in the short-form (SF)-36 physical component summary scale, a validated quality-of-life measurement. However, after 12 and 24 months, the difference in improvement between the two groups was no longer significant [60,61]. The changes in pain (SF-36 bodily pain) and quality-of-life (EuroQuol self-report) scores, predefined secondary endpoints, were statistically significant (favoring kyphoplasty) at all time points [61].

Adverse effects — Vertebroplasty and kyphoplasty are considered safe but are not without risk. Short-term complications occur predominantly due to extravasation of the cement and may include increased pain and damage from heat or pressure to the spinal cord or nerve roots [62], and rarely cement embolization [63]. Possible long-term complications may include local acceleration of bone resorption caused by the treatment itself or by foreign body reaction at the cement bone interface. An increased risk of fracture in adjacent vertebrae has been debated but has not been proven in randomized trials. Polymethylmethacrylate (PMMA) cement is not as biologically inert as initially considered, and it has been associated with bone necrosis surrounded by fibrotic tissue, foreign body reaction, and neovascularization [64].

●Extravasation of cement – Extravasation of cement has been reported in 11 to 73 percent of vertebroplasty procedures [65] and less commonly with kyphoplasty, although extravasation is not clinically relevant unless it occurs in the spinal canal or neural foraminae, both of which are very rare.

●Pulmonary cement embolism – There have been several early case reports of pulmonary embolization of the cement during vertebroplasty [63]. Pulmonary emboli were noted on chest radiography in approximately 5 percent of patients in one series of 65 procedures and in 23 percent of patients in a series of 78 procedures [66,67]. None of the radiographically detected embolic events produced symptoms. In one of these studies, cement leakage into the inferior vena cava was the only significant risk factor for developing pulmonary cement embolism [67].

●Infectious complications – Infectious complications like pyogenic spondylitis and osteomyelitis following vertebral augmentation are both extremely rare [68-70].

●New fractures – In most [42,49,51,60], but not all [48], randomized trials, the incidence of new fractures was not significantly different in the vertebroplasty/kyphoplasty group when compared with controls. However, retrospective reviews of patients treated with vertebroplasty found a high rate of new vertebral fractures [71-74].

In a population-based retrospective cohort study of patients with previous vertebral compression fracture, 48 patients who received vertebroplasty or kyphoplasty were compared with 164 patients who did not. Treated patients had a significantly greater risk of subsequent vertebral compression fractures than the comparison group (odds ratios [ORs] 6.8, 95% CI 1.7-26.9 and 2.9, 95% CI 1.1-7.9, for secondary fractures occurring within 90 and 360 days of the procedure, respectively) [75]. In a systematic review of 24 observational studies, low BMD, intradiscal cement leakage, and vertebral height restoration were identified as important risk factors for new vertebral compression fracture after vertebroplasty [76]. In a subsequent trial, age >80 years, cement leakage, vitamin D deficiency, and need for procedures at multiple levels were identified as important risk factors related to the development of new vertebral fracture after vertebroplasty [77].

Bracing — We do not typically use bracing for the management of pain in patients with osteoporotic compression fractures. If a brace is used to relieve pain, it should be used in the acute and subacute phases of treatment for pain control, but not longer, as atrophy of the core musculature may occur with prolonged use. The brace selected needs to align with the level of the fracture. For example, a lumbar brace will have no effect on a thoracic fracture. Thoracic fractures may require a custom brace to adequately stabilize a fracture.

Small randomized trials evaluating back bracing for improving pain and mobility in patients with osteoporotic compression fractures do not show efficacy [36,78,79].

Exercise — An exercise program can be initiated when pain has diminished. Exercise has beneficial effects on BMD in pre- and postmenopausal women and may also be beneficial in men. Exercise regimens in older adult patients who have had a vertebral fracture have been shown to decrease the use of analgesics and improve quality of life in some, but not all, studies [80-82]. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women" and "Etiology of osteoporosis in men", section on 'Lifestyle factors'.)

Aquatic therapy is an excellent means of pain management in our experience. Use of the Arthritis Foundation aquatic program hastens the relief of pain and can also lead to early resumption of activity; begin as soon as patients can tolerate the movements. Hyperextension exercises may relieve pain and prevent kyphosis (figure 5) [83]; we use this routinely in older adult patients with osteoporosis. The posterior pelvic tilt is another useful exercise (figure 6).

Treatment for osteoporosis — Antiresorptive therapy with bisphosphonates or other osteoporosis therapy should be part of the treatment plan. Unfortunately, the majority of patients with spine, hip, and distal radius fractures do not receive evaluation and treatment for underlying osteoporosis [84]. (See "Treatment of osteoporosis in men" and "Bisphosphonate therapy for the treatment of osteoporosis".)

Lifestyle changes are essential. Smoking is a risk factor for osteoporosis. Alcohol abuse in older adults increases the risk of falling. Daredevil acts that predispose to fracture (eg, parachuting, trampoline exercise), sedentary inactivity, a low calcium diet, and tobacco use are important considerations for change. (See "Osteoporotic fracture risk assessment" and "Overview of the management of low bone mass and osteoporosis in postmenopausal women", section on 'Lifestyle measures to reduce bone loss' and "Calcium and vitamin D supplementation in osteoporosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteoporosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Vertebral compression fracture (The Basics)" and "Patient education: Kyphosis in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical manifestations – Acute episodes of significant vertebral body compression, which may occur after sudden bending, coughing, lifting, or a fall, are associated with pain. The pain is usually well localized to the midline spine but often refers in a unilateral or bilateral pattern into the flank, anterior abdomen, or the posterior-superior iliac spine. In contrast, osteoporotic vertebral compression that occurs slowly over time is often asymptomatic. In other patients, the presence of vertebral fractures may become apparent because of height loss or kyphosis. (See 'Clinical manifestations' above.)

●Evaluation – The evaluation of an osteoporotic compression fracture includes a history and physical examination to assess for neurologic findings, which may necessitate further imaging and consultation with a spine surgeon. In addition, MRI is used to date the acuity of fractures, when such information is important (eg, determining whether a fracture is a source of recent-onset back pain). MRI and CT can be used to assess for retropulsion (axial images); if patient cannot get MRI (eg, pacemaker, automatic implantable cardioverter-defibrillator [AICD]), then bone scan can assess the metabolic activity/age of the fracture. Laboratory evaluation to assess for malignancy (such as multiple myeloma) and secondary causes of osteoporosis may be indicated. (See 'Evaluation' above.)

●Our approach to management – The management of an acute osteoporotic vertebral compression fracture includes pain control, activity modification, education, and treatment of the underlying osteoporosis. (See 'Overview' above.)

•Mild to moderate pain – For patients with mild to moderate pain, acetaminophen, ibuprofen, or naproxen is often sufficient for initial management. We initiate intranasal calcitonin early in the course of therapy. Calcitonin is not effective immediately; therefore, initiating it with acetaminophen, ibuprofen, or naproxen allows the oral analgesics to provide some pain relief until the calcitonin becomes effective. (See 'Mild to moderate pain' above and 'Calcitonin' above.)

If there is inadequate analgesia after one to two weeks of initial management, an immediate-release opioid, a mu agonist (eg, tramadol, tapentadol), or a mixed agonist/antagonist like buprenorphine are options. (See 'Mild to moderate pain' above and 'Oral analgesics' above.)

•Severe pain – Patients with severe pain from an acute (0 to 4 weeks) vertebral body fracture typically require opioids at the outset. When opioids are required to control pain from vertebral compression fractures, we typically initiate treatment with an immediate-release opioid combined with low-dose acetaminophen. If the pain is incapacitating, hospital admission and parenteral analgesia for pain management may be necessary. (See 'Severe pain' above.)

For patients with incapacitating pain from acute and subacute vertebral compression fractures who are unable to taper parenteral or transition to oral opioids within seven days of admission or have intolerable sedation, constipation, or delirium from this therapy, we suggest vertebral augmentation rather than continued medical management (Grade 2C). This is typically performed during the initial hospitalization. (See 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)' above.)

Vertebroplasty and kyphoplasty appear to perform similarly. Vertebroplasty is performed when there is little to no compression of the vertebral body, but MRI shows bone marrow edema consistent with fracture. It does not rely on the performance of a balloon system and is less expensive than kyphoplasty. Kyphoplasty relies on the use of a balloon tamponade system that can have technical difficulties, but it may partially restore vertebral height. (See 'Vertebral augmentation procedures (vertebroplasty and kyphoplasty)' above and 'Selection of procedure' above.)

•Persistent pain – Management options for patients with persistent pain (greater than six weeks of medical management) include continued medical management or vertebral augmentation. Continued medical management is the best option for patients who have noticed some improvement in pain and who are able to tolerate, maintain, or taper opioids and begin a physical therapy program. For those who are not satisfied with the level of symptomatic relief (eg, even with higher doses of opioids), are unable to perform the activities of daily living, or are not tolerating opioids (constipation, confusion, urinary retention), we suggest vertebral augmentation rather than continued medical management (Grade 2C). (See 'Persistent pain' above and 'Selection of patients' above.)

•No role for skeletal muscle relaxants – We suggest not using skeletal muscle relaxants for the acute management of pain in patients with osteoporotic compression fractures (Grade 2C). (See 'Muscle relaxants' above.)

•Limited role for bracing – We do not typically use bracing for the management of pain in patients with osteoporotic compression fractures. If a brace is used to relieve pain, it should be used in the acute and subacute phases of treatment for pain control, but not longer, as atrophy of the core musculature may occur with prolonged use. (See 'Bracing' above.)

●Long-term management of osteoporosis – Patients with osteoporotic compression fractures are treated with lifestyle and pharmacologic therapy to prevent subsequent fractures. (See "Overview of the management of low bone mass and osteoporosis in postmenopausal women" and "Treatment of osteoporosis in men".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David Richard Walega, MD, who contributed to earlier versions of this topic review.