Strategies for Treating Osteoporosis and Its Neurologic Complications

Osteoporosis is a disorder characterized by low bone mass and microarchitectural deterioration with resulting compromised bone strength and increased risk of fracture.1 The World Health Organization defines osteoporosis based on T-scores, which reflect bone mineral density (BMD) relative to mean BMD for healthy 25-year-old same-sex populations. A T-score between 0 and 21 is considered normal density, a score between 21 and 22.5 indicates osteopenia, and a score of less than 22.5 signifies osteoporosis.2 Severe osteoporosis is defined as a T-score of less than 22.5 combined with a fragility fracture.2Osteoporosis is divided into primary and secondary disease. Primary osteoporosis is not associated with other medical conditions and is divided into 2 types: postmenopausal osteoporosis attributed to estrogen deficiency (type 1), and senile osteoporosis attributed to inadequate lifetime calcium intake (type 2).3 Secondary osteoporosis occurs with chronic conditions or medications that contribute to accelerated bone loss. The most common cause of secondary osteoporosis is prolonged glucocorticoid use.4 Appropriate history, physical examination, and laboratory tests should be performed to evaluate secondary osteoporosis.In the United States, an estimated 7.8 million individuals have osteoporosis.1 One of 2 white women will have an osteoporotic fracture at some point in her lifetime.1 The majority of these will be vertebral fractures. Approximately 700,000 osteoporotic vertebral fractures were reported in 1995.5 From age 50 onward, the lifetime risk of sustaining a fragility fracture for white women and men is 40% and 13%, respectively.5 The majority of these fractures are self-limited, commonly responding to time, bed rest, analgesics, and bracing. However, approximately 150,000 vertebral fractures continue to cause significant pain.3 After having 1 vertebral fracture, the risk of occurrence of another fracture can increase up to 12.6-fold.6Osteoporotic vertebral compression fractures (OVCFs) are predominantly located in the thoracolumbar region, with fractures rarely above T6.7 Three fracture types are commonly reported: wedge compression, biconcave, and crush.8,9 Wedge compression fractures are the most common, although patients may present with various combinations of the different types.9 The anterior-superior endplate is predisposed to compressive fracture because of increased trabecular spacing and disconnectivity.10With thoracic wedge compression fractures, anterior translation of the upper body and head occurs.11 The increased kyphosis results in increased forces on the anterior column from the forward bending movement and especially affects the thoracolumbar junction.11,12 The progressing kyphosis may exacerbate the risk of adjacent segment fracture, particularly in the thoracolumbar junction.11-15NEUROLOGIC COMPLICATIONSAlthough the compression fracture is the most common, the burst fracture (or axial compression fracture) is another fracture type that is important to recognize. The burst fracture can result in instability and neurologic compromise. Furthermore, disruption of the posterior vertebral wall can influence the practitioner's decision to proceed with percutaneous vertebral augmentation because this disruption increases the risk of extrusion of cement into the spinal canal.16Because of the low bone density associated with osteoporosis, identifying a fracture of the posterior vertebral wall may be difficult on plain x-ray films. Retropulsion of the posterior wall and widening of the pedicles are consistent with a burst fracture. MRI is not only helpful in determining whether a fracture is acute, chronic, or pathologic but also can evaluate for retropulsion of the posterior wall and resultant spinal canal compromise. However, thin-slice CT is the imaging modality of choice for evaluating the posterior wall.The individual suffering from single or multiple fractures can experience significant pain, decreased quality of life, and depression.1,13 With repeated fractures, kyphosis can progress, resulting in the characteristic dowager hump. Alteration of sagittal balance has been proposed as a cause of continued pain, increased risk of adjacent segment fracture, and impaired balance.15 Furthermore, with increasing kyphosis, the ribs can abut the iliac crests, compressing abdominal organs. This can lead to early satiety and subsequent poor nutritional intake. Compression of the abdominal contents also can affect diaphragmatic excursion. Forced vital capacity is reduced 9% with each thoracic compression fracture.17 Vertebral fragility fractures are associated with a 23% to 43% increase in mortality among women,18 as well as with increased fear, anxiety, and depression.19In the management of acute OVCF, treating the acute pain and functional impairment is inadequate in preventing future fractures and morbidity. Reversible causes of secondary osteoporosis need to be identified, as do reversible risk factors, medication, fall reduction strategies, and exercise in patients with primary osteoporosis. Bracing, vertebral augmentation, and surgical treatments also play roles in treatment.BMD is affected by irreversible factors, such as genetics,20 race, sex, and age. The National Osteoporosis Foundation also reports the following major risk factors for fracture: fragility fracture in a first-degree relative, body weight of less than 127 lb, smoking, and oral corticosteroid therapy for longer than 3 months. Additional factors include advancing age, estrogen deficiency in those younger than 45 years, lifelong low calcium intake, excessive caffeine intake, alcohol intake of more than 2 drinks per day, dementia, impaired vision, recent falls, low physical activity, and poor health.1 Excessive vitamin D intake also can deleteriously affect BMD,21 along with prolonged bed rest.The patient treated for a vertebral fracture should be counseled regarding risk factors and behavior modification. She should have a proper diet with adequate vitamin D (400 to 1000 units/d) and calcium (1000 to 1500 mg/d) intake.19 Precautions to avoid falls should be taken, and an exercise program should be instituted.The patient with pain from an acute vertebral fracture should avoid prolonged bed rest. Bracing, calcitonin nasal spray, and analgesics should be used to control pain and allow early ambulation. Narcotic analgesics may be required, and the patient should be warned and monitored for potential adverse CNS depressant effects.MEDICATIONSPerimenopausal women may experience accelerated bone loss because of estrogen deficiency. Hormone replacement therapy (HRT) can prevent this bone loss and decrease vertebral fracture risk.19 Estrogen therapy needs to be weighed against the increased risk of coronary artery disease, cerebral vascular accidents, venous thromboembolism, and invasive breast cancer associated with HRT.4Bisphosphonates are potent antiresorptive agents that inhibit osteoclast-mediated bone resorption.22 Alendronate (Fosamax, Merck & Co), risedronate (Actonel, Aventis Pharmaceuticals), and pamidronate (Aredia, Novartis Pharmaceuticals) are the 3 available FDA-approved products. Pamidronate is typically used in the treatment of hypercalcemia of malignancy and Paget disease.4 It is usually given intravenously to patients who are unable to tolerate oral bisphosphonates.4 Alendronate was the first bisphosphonate approved by the FDA for treating osteoporosis. It and risedronate, a third-generation bisphosphonate, have been shown to improve BMD and reduce fractures in both the spine and hip.22-25Calcitonin reduces bone resorption by direct inhibition of osteoclastic function.26 Furthermore, a prospective, double-blind, placebo-controlled trial found that calcitonin reduced pain and allowed earlier patient mobilization than placebo in patients with acute OVCFs.27The latest medication approved for osteoporosis is parathyroid hormone (PTH). Unlike the previously described antiresorptive agents, PTH stimulates bone formation. Continuous infusion results in greater bone resorption than daily injections, although both methods encourage bone formation.28 Low-dose daily injections of synthetic PTH(1-34) can stimulate bone formation, increase BMD, and reduce the incidence of vertebral and hip fractures.28Recent strategies have included combining antiresorptive agents with medication to stimulate bone formation. Estrogen combined with PTH had an additive effect compared with estrogen alone, with increased BMD and fewer vertebral fractures.29BRACINGA paucity of literature exists on bracing for osteoporotic vertebral fractures. To our knowledge, 2 prospective randomized, controlled trials published in the English literature have been conducted.The first concerns a posture training support (PTS) versus a semirigid thoracolumbar orthosis (TLO).30 In this study, 45 women with osteoporosis were randomized into groups treated with postural exercise only, postural exercise and TLO, or postural exercise and PTS.The study found increased back extensor strength in the PTS group compared with the TLO group. In addition, better compliance was seen in the PTS group. No statistical significance for increased strength was found between the PTS group and the control group, which only engaged in an exercise program. The authors attribute this to the small sample size.31 The PTS was associated with pain reduction in 17 of 23 participants in a pilot study.31In the second prospective randomized trial, 62 osteoporotic women with kyphosis of more than 60 degrees and at least 1 vertebral fracture were randomized into a braced group or a nonbraced group. At 6 months, significantly increased back extensor strength, reduced kyphosis, decreased pain, reduced body sway, and improved function were seen in the braced group.32 However, these studies did not involve patients with acute OVCF.Bracing does have associated risks. Braces can restrict breathing, further compromising vital capacity in those with lung disease.30,33 The skin must be monitored for ulceration. Braces can be uncomfortable and burdensome for the elderly patient, which can result in poor compliance.Further muscle weakness and soft tissue contractures can occur. Some patients may become psychologically dependent on their brace as well. The decision to brace depends on balancing goals against risks. In addition, fracture type, age, and location will influence the need for and type of brace to use.NEUROLOGIC DEFICIT AND SURGERYIn the osteoporotic patient with a burst fracture, the clinician should follow the guidelines for burst fracture treatment. In the past, surgical treatment was typically recommended, but recent studies have supported nonsurgical treatment.34-37 In these studies, most patients with neurologic deficit had improved function (measured by Frankel grades); none experienced worsening of neurologic status.35,36 However, the presence of a neurologic deficit is, for many, an indication for surgical treatment. In these patients, a multidisciplinary approach to individualized treatment should include collaboration of a spine surgeon, physiatrist, physical therapist, and occupational therapist. Indications for surgery include a grossly unstable fracture with complete neurologic deficit, progressive neurologic deficit, progressive deformity, posterior column injury, greater than 50% loss of vertebral height with significant kyphosis, and severe instability.37The goals of nonsurgical burst fracture treatment through the use of bracing are immobilization, protection of neurologic structures, early ambulation, and pain mitigation. For burst fractures in the thoracic and upper lumbar region, bracing needs to control not only flexion and extension but also axial rotation and lateral bending.To achieve this, a custom-molded thermoplastic thoracic-lumbar-sacral orthosis (TLSO) is recommended for fractures from T6 to L3.36,38 The patient is braced for 12 weeks. During this time, the patient performs trunk extension exercises in the brace to avoid muscular atrophy. For fractures at L4 and L5, a TLSO with a hip spica is required to minimize motion.39 However, these braces are poorly tolerated. A custom-molded thermoplastic lumbar-sacral orthosis (LSO) is frequently used.37Bracing is recommended for wedge compression fractures with more than 30% loss of anterior height, which may have a greater risk for chronic pain and progressive deformity.12,40,41 The goal of bracing is to keep the spine in extension to unload the anterior column to reduce pain and prevent further kyphosis.To meet these goals, a hyperextension brace is recommended. For fractures between T6 and L3, a cruciform anterior spinal hyperextension, or Jewett, brace is used. All these braces are based on 3-point fixation with pads anterior over the pubis and sternum and a counterforce pad posterior over the apex of the fracture. For fractures between L3 and L5, a custom-molded thermoplastic LSO is used.40 Patients are braced for 6 to 12 weeks.For wedge compression fractures with anterior height loss of 30% or less, bracing is not required.40 If bracing is for comfort, a hyperextension brace, PTS, semirigid TLO, or LSO may be used. The PTS unloads the anterior column by positioning the spine in extension and is well tolerated.30,31If a decision is made not to brace, the patient with an acute fracture should be followed closely. A repeated spot lateral plain x-ray film of the fracture should be obtained to rule out any progressive deformity that would then require bracing or vertebral augmentation. Beware of the minimal superior endplate fracture, which may progress to vertebral plana and cause chronic pain.40,42EXERCISE AND REHABILITATIONExercise is an effective prevention and treatment strategy for osteoporosis that can increase BMD, muscle mass, and strength in elderly populations.43 Exercise also may have positive effects on mobility, posture, and balance, thus decreasing the risk of falls and fracture.1 Designing an appropriate therapeutic exercise program for patients with osteoporosis requires a specific evaluation that identifies the patient's functional limitations, specific equipment needs, and environmental barriers requiring modification.44In the patient with osteoporosis who sustains an acute OVCF, initial treatment should reduce pain, increase mobility, and improve functional limitations.45 Thermal modalities, such as cold packs, should be considered in the early stages to reduce pain and inflammation.46 Ambulation and gait training with assistive devices, used as necessary, are essential in the acute stage to promote early mobility and to return the patient to activities of daily living.Following the acute stage, superficial heat and gentle range of motion exercises can be used to reduce muscle spasm, alleviate pain, and maintain mobility.46 After the first 4 to 6 weeks, combined pharmacologic and therapeutic protocols should alleviate pain to the extent that a functional rehabilitation program can be started.47Some researchers have shown that spinal extension exercises are more appropriate than flexion exercises in strengthening spinal extensors and preventing further vertebral fractures.48 The researchers found that spinal flexion exercises actually can increase the risk of vertebral compression fractures because of increased flexion forces on the vertebrae.4,48 Caution should be used with exercises that involve rotation of the spine and put stress on the vertebral body, increasing fracture risk.49Extension exercises including but not limited to "prone on elbows," "prone bilateral upper extremity flexion," "prone hip extension," and "prone upper body extension" may be more appropriate in this patient population. Extension exercises improve spinal extensor strength, which, in turn, improves vertebral BMD43,50,51 and posture, inhibiting the progression of dorsal kyphosis.51,52Other researchers also found that isometric abdominal and neutral spine strengthening exercises are more appropriate than pelvic tilts into flexion or abdominal crunches, which flex the spine.51 A pain-free, neutral spine position should be the basis for trunk stabilization programs. The patient can perform these exercises in a supine position, seated on a physioball, or standing. Trunk stabilization exercises allow the patient to strengthen the abdominal and trunk musculature in functional positions without increasing vertebral fracture risk. They also help the patient maintain proper posture.Progressive resistive exercise programs that focus on strengthening the large muscle groups also have been associated with an increase in BMD in elderly persons.50,53-55 Research suggests that benefits to BMD are specific to the working muscles and the bones to which they attach.55 Lumbar spine BMD improves with strengthening of the knee flexors and extensors.53,54 Exercise protocols to increase strength and mass of the large muscle groups in elderly persons typically have intensities and frequencies of 65% to 80% for 1 repetition maximum and 3 sets of 8 to 10 repetitions, respectively.43,49,50,56Large-muscle exercises can include chest press, leg press, biceps curl, triceps extension, hamstring curls, and calf raises. These exercises not only build muscle strength, slow bone loss, and increase bone mass but also reduce incidence of falls.51 Resistance training has a profound effect on activities of daily living, such as climbing stairs, carrying groceries, and rising from a chair.55 Weight-bearing exercises have been shown to increase lumbar bone mineral content in postmenopausal women.57 These exercises can include walking, jogging, and stair climbing.Some researchers showed that patients with kyphosis had more postural sway and used hip strategies more than ankle strategies to maintain balance than did patients without kyphosis.58 Exercises that improve balance include "single leg balance," "tandem stance," and "side-stepping over cones." Balance exercises have been reported to reduce falls59 and thus reduce fracture risk. It is also appropriate to evaluate a patient's home to eliminate or modify environmental barriers that can contribute to falls.PAIN REDUCTION THROUGH VERTEBROPLASTYFor those patients whose pain persists despite conservative treatment or who demonstrate progressive vertebral body collapse with continued findings of bone marrow edema on MRI, percutaneous vertebral augmentation may be an alternative. Vertebroplasty was pioneered by Galibert, Deramond, and others in 1984 for the treatment of vertebral hemangioma.16 The procedure consists of percutaneous instillation of acrylic cement into the fractured vertebra usinga transpedicular or extrapedicular approach. The goal of vertebroplasty is to reduce pain, stabilize the fracture, improve patient function, and restore mobility.Kyphoplasty was developed later with the added goals of fracture reduction and lower pressure injection. Kyphoplasty uses a balloon to create a void within the vertebral body, reduce the fracture before instillation of the cement, and restore sagittal plane alignment. The mechanism for pain relief from either procedure is not known at this time.While not the primary goals of the procedure, restoration of height and reduction of kyphosis have been shown with vertebroplasty. In a prospective study, patients with OVCF and an intravertebral cleft had 8.4-mm (106%) height restoration and 40% decrease in kyphosis postvertebroplasty.60 Another study evaluated closed reduction vertebroplasty in single-level OVCF and found anterior and mid-body height restorations in 81% and 76% of patients, respectively, with mean corrections of 57% and 61%, respectively. A mean kyphotic reduction of 12.5 degrees occurred in 71.5%.61In prospective studies, kyphoplasty has resulted in decreased pain in 89% to 97% of the participants.62-64 In the only prospective controlled study, visual analog scale pain scores for participants with vertebral compression fractures decreased 82% in the kyphoplasty group, compared with 42% in controls.65 Fracture reduction has occurred in 90% to 92% of these patients,62,66 with a mean kyphosis correction of 5 to 8.8 degrees62,65-67 or 47.7% reduction,68 with an anterior height correction of 4.1 to 4.6 mm and a midvertebral body height correction of 3.9 to 4.8 mm.62,69,70 Functional improvement on the Oswestry Disability Index at 1 to 2 years postkyphoplasty ranged from 53% to 57%.62-66,69,70Complications associated with both vertebroplasty and kyphoplasty have included death, cardiac arrest, cement pulmonary embolism, paralysis from cement intrusion into the spinal canal, and pedicle fracture.70,71-78 Also, epidural hematoma, ileus, diskitis, osteomyelitis, pneumothorax, hypotension, urine retention, and dural puncture have been reported with kyphoplasty.63,70,71 Complications, including allergic reactions and urine retention, have been reported with vertebroplasty.61Much of the concern about vertebral augmentation has been related to cement leakage resulting in pulmonary embolism or spinal canal compression. The vast majority of cement leakage is asymptomatic. In most prospective studies, cement leakage was noted during fluoroscopy or on plain films. In these studies, the incidence of cement leakage reported for vertebroplasty ranged from 4.5% to 26%.60,62,64 For kyphoplasty, the range was 2% to 17.8%.62,63,65,68,70,79 However, CT is more sensitive in detecting cement leakage.Cement extrusion into the vertebral venous system may be reduced by raising intrathoracic venous pressure, thus increasing vertebral venous pressure.80Another concern has been that alteration of spinal biomechanics after augmentation may lead to adjacent fractures.81 Vertebroplasty results in a return to prefracture strength for the fractured vertebra, but the spinal column may weaken in the event of adjacent fracture.82 Kyphoplasty has been reported to increase the risk of adjacent fracture by 21% within 60 days after the procedure.83Reported risk factors for an adjacent fracture following vertebral augmentation are corticosteroid-dependent osteoporosis, cement leakage into the disk, thoracolumbar junction fracture location, and restoration of height with augmentation.81,84-86 The report that increased height restoration because of augmentation is a risk factor for adjacent fracture, however, is contrary to current theories. A kyphotic deformity is associated with anterior displacement of the center of mass, which increases the forward-bending movement. This is postulated to result in increased stress on the adjacent vertebrae, resulting in fracture.15In addition, restoration of sagittal balance may protect against the complications of progressive kyphosis, which are reduced vital capacity, early satiety, protruberant abdomen, impaired balance, chronic back pain, depression, poor self-esteem, and reduced quality of life. In the context of the natural history of osteoporosis, adjacent fractures have been reported in 58% of patients with more than 1 fracture.87 Further study is required to determine whether the incidence of an adjacent fracture is secondary to altered biomechanics from augmentation or the natural history of OVCFs with deformity.Other surgical options include the use of OptiMesh (ICEM CFD Engineering), a transpedicular or extrapedicular percutaneous internal fixation fusion device that recently has been approved by the FDA for use in compression fractures resulting from trauma, tumor, or metabolic causes such as osteoporosis. Instead of cement, this system uses demineralized cancellous bone packed within a sack that allows for bony ingrowth and maintains structural support. This creates a vertebral body with a modulus of elasticity similar to bone (not cement). In theory, it could reduce the risk of adjacent fractures.Its use will not likely change the natural risk of another osteoporotic fracture but may be of benefit in the younger patient undergoing vertebral augmentation. Spine surgeons anecdotally have reported that pain is an issue where there is fragmented vertebral cement, requiring corpectomy and stabilization (J. Shook, Loma Linda University, unpublished data, 2005). OptiMesh does not pose the disadvantage of potential cement osteolysis.Although limited data are available on OptiMesh and its efficacy, especially in the difficult-to-treat patient population with osteoporosis, various studies are currently being performed.Christopher W. Huston, MD, Duane D.H. Pitt, MD, and Camille Lane, PT, are all associated with the Orthopedic Clinic Association in Phoenix.

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