Osteoporosis and fractures after CNS injury

Author(s): Diane Schretzman Mortimer, MD, Kerri Chung, DO

Originally published:10/22/2013

Last updated:08/18/2016

1. DISEASE/DISORDER:

Definition

Osteoporosis literally means “porous bones.” It is a disorder of bone and mineral metabolism characterized by low bone mineral density (BMD). The World Health Organization (WHO) defines it as a BMD of 2.5 standard deviations or more below the mean peak bone mass as measured by dual-energy X-ray absorptiometry (DXA).

Etiology

Osteoporosis frequently develops after the onset of disability and results from the imbalance of bone formation and resorption. Many individuals with central nervous system (CNS) injury are at risk for osteoporosis, including individuals with spinal cord injury (SCI), stroke, multiple sclerosis (MS), Parkinson’s disease, cerebral palsy (CP), and brain tumors.

Epidemiology including risk factors and primary prevention

Immobility is the greatest contributing factor to the development of osteoporosis in CNS injury. Other risk factors include mechanical unloading and duration since onset of disability. Medications including heparin, warfarin, glucocorticoids and anticonvulsants may also contribute. Most people with SCI develop osteoporosis, but the degree of bone loss is greater with higher neurological level and more complete injuries. For example, individuals with paraplegia have 16% more bone density in their upper extremities than do those with tetraplegia.

Patho-anatomy/physiology

Reduced mechanical stress on bone, primarily through decreased weight bearing, inhibits osteoblast-mediated bone formation and accelerates osteoclast-mediated bone resorption. Osteoporosis in SCI is also mediated by hormonal changes, including parathyroid (PTH) and thyroid hormones, and blunted sympathetic activity. These autonomic changes cause dilation of bony intravenous shunts and vascular stasis which is thought to contribute to an imbalance of bone formation and resorption. Post-stroke osteoporosis is more evident on the paretic side and preferentially involves the upper extremities. In adults with CP, osteoporosis is not primarily from a loss of bone minerals, but instead from a failure to accrue bone mass in childhood and adolescence.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Disease progression differs by the type of CNS injury. Patients with SCI experience most bone loss in the first 12- 18 months, but loss continues at a slower rate afterwards. Individuals with motor complete SCI have regional bone loss of almost 1% of bone mineral density per week for the first several months post injury. By 10-12 years, the pelvis and lower extremities suffer approximately 50% bone demineralization, and 21% in the upper extremities, but there may be a net gain in the trunk. In stroke, bone loss reaches a maximum at 3-4 months and then stabilizes. Recovery of bone density has been seen in patients who recover ambulation. Individuals with progressive MS have more severe bone loss than those with a relapsing-remitting disease course.

Specific secondary or associated conditions and complications

The major complication of osteoporosis is fracture, which can lead to increased morbidity, mortality, and healthcare costs. Those with SCI are 104 times more likely to have a fracture by the age of 50 than the general population. The incidence of lower extremity fractures in people with SCI is as high as 34% and is greatest at the supracondylar region and the proximal tibia. SCI patients with fractures are at increased risk for osteomyelitis, pressure ulcers, and autonomic dysreflexia. Post-stroke patients have a risk of hip fracture 1.5 to 4 times higher than healthy individuals of comparable age. Fractures more commonly involve the plegic side and are associated with the development of additional strokes, increased mortality, increased hospital length of stay, and fewer discharges home. Patients with multiple sclerosis have a 20-40% increased risk of fracture compared to the general population. Finally, patients with Parkinson’s disease have a higher incidence of hip fractures than the general population and experience a decline in independence after fracture.

2. ESSENTIALS OF ASSESSMENT

History

Assessment should include a comprehensive evaluation of current health status and osteoporosis risk factors. It is necessary to identify any additional secondary causes of osteoporosis, including thyroid disease, parathyroid disease, renal failure, chronic liver disease, inflammatory bowel disease, anorexia, amenorrhea/menopause, hypogonadism, and any cancer managed with chemotherapy or radiation. Other risk factors, including hereditary disposition, smoking and alcohol use, should be ascertained. For individuals with CNS injury, particular attention should also be paid to immobility, degree of motor impairment, and duration of disability. Past and current medications should be reviewed to determine possible contributing factors. Finally, consideration should be made regarding pre-existing osteoporosis and history of low impact fractures.

Physical examination

There are no specific physical exam findings for osteoporosis. However, localized edema and erythema may indicate an underlying fracture in asymptomatic insensate patients.

Functional assessment

Functional assessment should focus on evaluation of fall risk. Factors to consider are mobility, balance, urinary incontinence, visual problems, polypharmacy, and environmental safety. Falls are extremely common after CNS injury and greatly increase the likelihood of fracture. One study showed 73% of individuals with a stroke experience a fall within 6 months of hospital discharge. Ambulation with an inadequate assistive device or on uneven surfaces, as well as poor technique with transfers, increase fall risk.

Laboratory studies

No laboratory tests exist for the diagnosis of osteoporosis, but many tests may identify secondary causes. Clinicians should consider obtaining a complete blood count, chemistry panel, thyroid stimulating hormone (TSH), PTH, ionized calcium, liver function tests, bone specific alkaline phosphatase, 24-hour urinary calcium, 25-hydroxyvitamin D3, and gonadal hormones. Hydroxyproline is a urinary marker of bone resorption and may be useful for early identification.

Imaging

DXA is currently the criterion standard for the evaluation of BMD. DXA consists of 2 x-ray beams with different energy levels focused on a specific area of bone. Soft tissue is subtracted out and the BMD can be determined by the absorption of each beam by the bone. BMD is reported as a T- or Z-score as appropriate.

T-score: compared to control subjects at peak BMD

  1. 1 to 2.5 SD indicates osteopenia
  2. < 2.5 SD indicates osteoporosis
  3. < 2.5 SD with fragility fracture(s) indicates severe osteoporosis

Z-score: compared to patients matched for age and sex

  1. < 2.0 SD is below the expected range for age
  2. 2.0 SD is within the expected range for age

While used regularly to visualize fractures, plain radiography is less helpful for detection of bone loss, as 30% of bone density must be lost before changes can be detected. They may, however, be used to assess for fractures, particularly in patients with decreased or absent sensation. Quantitative computed tomography (QCT) can be used to assess bone architecture, but is mostly a research tool and is not routinely available in the clinical setting.

Supplemental assessment tools

Combining clinical risk factors with BMD is thought to provide the best estimate of fracture risk, compared to each assessment alone.

Early predictions of outcomes

Risk factors for fractures should be minimized. Methods include prevention and treatment of osteoporosis, and proper assessment of fall risk.

Environmental

Home evaluation and modification are extremely important for fall prevention. Patients and families can be asked to complete a self-assessment form, or a formal evaluation can be performed by a member of the therapy team.

Social role and social support system

Awareness of the possibility of bone loss and fracture by the patient, family, clinician, and other members of the rehabilitation team is essential for the development of a comprehensive prevention and treatment approach.

Professional Issues

Osteopenia and osteoporosis are very common in adults with disability participating in rehabilitation; nevertheless, focus on prevention and treatment is less prevalent. Even in a specialized stroke management center that was reviewed, it was reported that relatively few patients were taking osteoporosis medications and supplements compared to what would be expected based on known prevalence of osteoporosis in this populations.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

There are no established guidelines for treating osteoporosis in CNS injury. Treatment of established osteoporosis should focus on treating or eliminating secondary causes of osteoporosis, modifying lifestyle factors, developing an appropriate exercise/rehabilitation program, dietary supplementation, and specific pharmacologic treatments, typically with anti-resorptive agents. Individuals should receive counseling regarding reducing alcohol intake, smoking cessation, and modifying caffeine consumption, if appropriate. Early weight-bearing exercise may be considered, although it has not been shown to be effective in SCI.

At different disease stages

Prevention of bone loss is thought to be more effective than treatment of established osteoporosis. Clinicians should consider proper nutrition, lifestyle modifications, supplementation, and weight-bearing exercise in all individuals with CNS injury early after diagnosis. Specific attention should also be paid to reduction of fall risk, with consideration of mobility aids and environmental modifications. Additionally, initiation of anti-resorptive agents should be considered. Bisphosphonates have shown most potential for the prevention of bone loss when used early in the post-injury period, but length of treatment and effect on fracture rates remain unknown. In SCI, passive weight bearing has been largely ineffective, but functional electrical stimulation (FES) of at least 1.5 times body weight for 30 minutes, 3 times weekly, has been shown to be beneficial in some studies. Weekly alendronate has been shown to prevent total body and hip bone loss at 1 year post-injury, and 2 years of daily alendronate prevented ongoing bone loss at the distal tibia, but long-term effectiveness remains unknown. In elderly patients with stroke, early return to walking and bisphosphonate treatment within a few days to 5 weeks after the onset of stroke may prevent bone loss, particularly on the paretic side, but the effect on fractures remains unclear.

Coordination of care

Bone health after CNS injury is best approached by a multidisciplinary team inclusive of a physiatrist, occupational therapist, physical therapist, the patient and family.

Patient & family education

Clinicians should discuss bone loss early after CNS injury, both with patients and their families. Particular emphasis should be placed on fall prevention and reducing fall risk. Increased risk of osteoporosis as an adverse effect of medications including steroids should also be discussed, so families can monitor and assist to prevent overuse.

Emerging/unique Interventions

BMD measurement using DXA has been shown to be the single best predictor of fracture at a particular site. Traditionally, DXA measurements are obtained at the lumbar spine, femoral neck, total hip, and distal radius. In individuals with SCI, measurements at the distal femur and proximal tibia are also recommended, as these are the most common areas of fracture. DXA can also be used to monitor disease progression and response to therapy. The International Society of Clinical Densitometry (ISCD) recommends monitoring response to treatment every 1-2 years at the same facility, with the same densitometer, using the same acquisition, and analysis protocols.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Referral to a specialist should be considered when osteoporosis leads to uncontrolled pain, if significant bone loss is refractory to treatment, or with development of fractures. Fractures in SCI patients, in particular, often do not need surgical intervention, as precise reduction may not be necessary and the bones may be too fragile for internal fixation.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Recent research has been focused on using bone turnover markers to monitor disease progression and response to treatment in osteoporosis. Examples of these markers include bone-specific alkaline phosphatase, osteocalcin, and c-telopeptide. In SCI, sclerostin is both a mediator of bone loss and an osteoporosis biomarker. Fat-bone interactions may contribute. Emerging therapies include anti-sclerostin antibodies, inhibitors of members of the transforming growth factor β family, and inhibitors of cathepsin. Inhibitors of transforming growth factor β family, part of a class of osteoanabolic agents, to preserve bone mass after paralysis. Clinical trials for cathepsin K inhibitors are ongoing for postmenopausal osteoporosis. These inhibitors are critical to resorption of bone by the osteoclast, therefore, may slow bone loss after SCI.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

While there is limited research on the treatment of osteoporosis in SCI, there is even less information available for Parkinson’s disease, stroke, ALS, CP, brain tumors and other CNS injuries. Additional studies should focus on these important disease processes. Furthermore, fracture incidence as a primary endpoint may have more clinical significance than bone loss.

REFERENCES

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Original Version of the Topic:

Marika Hess, MD, Timothy Tiu, MD, Jayne Donovan, MD. Osteoporosis and fractures after CNS injury. Publication Date:2013/10/22

Author to Disclose

Diane Schretzman Mortimer, MD
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Kerri Chung, DO
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