Within a short time after neurologically complete motor types of spinal cord injury (SCI), patients lose bone mineral density (BMD) at an estimated rate of 1% per week. Continued bone loss occurs for at least 3 to 8 years’ post-injury, although the process slows after the first year following an SCI.1 The rate of bone loss observed in SCI is much greater than that associated with other forms of immobilization that do not result in paralysis. For example, bone loss due to microgravity is estimated at 0.25% per week, bed rest at 0.1% per week, or postmenopausal women who are not taking medications to prevent bone resorption at 3% to 5% per year.1
The Bottom Line
- Rapid bone loss occurs at regional sites shortly after injury in individuals who sustain neurologically complete motor types of spinal cord injury, with progressive bone loss continuing for a number of years following the injury.
- Persons affected by a spinal cord injury are at a 5- to 23-fold higher risk for fractures as well as numerous complications and increased risk of mortality.
- Pharmacotherapy combined with mechanical interventions may offer the greatest benefit to patients with SCI to reduce their risk of bone loss, osteoporosis, and fractures.
The sudden skeletal unloading resulting from an acute SCI provokes significant changes in the functional relationship of osteoblasts and osteoclast. There is an increase in the function of both osteoclasts and osteoblasts immediately following the injury. During subsequent months, the formation of osteoblastic bone declines dramatically, while there is a substantial increase in trabecular osteoclastic resorptive surfaces. Clinical indicators of these changes include evidence of hypercalciuria and elevations in markers of bone resorption. Increased clearance of calcium by the kidneys also often occurs in response to the sudden and rapid onset of bone resorption; evidence of this is seen in increased levels of serum ionized calcium. This, in turn, results in the suppression of parathyroid hormone (PTH), further raising levels of calciuria. Individuals with SCI are also at risk for vitamin D deficiency, which can interfere with the absorption of calcium in response to therapeutic interventions to suppress bone resorption.1
An ongoing, prospective, observational study of patients with recent SCI evaluated the pathophysiology and risk factors for the loss of BMD, with data available from the 12-month follow-up evaluation for the first 35 patients. There was a substantial and statistically significant loss of BMD compared to baseline at the proximal femur, with a mean BMD loss of -21.54% (±6.84) and a loss of -18.8% (±5.09) at the femoral neck. BMD changes were negligible for the lumbar spine at 0.37% (±4.97). Densitometric osteoporosis (OP) was detected in 35% of patients at 6-months and 52% at 12-months post-injury.2
Patients who developed OP had significantly lower BMD values at the femur and lumbar spine as well as elevated markers of bone turnover at baseline. However, there were no significant differences in vitamin D levels, PTH serum levels, age, BMI, use of tobacco or alcohol, or characteristics of the injury, such as type, level, or time elapsed since injury. Significant risk factors for the development of OP based on multivariate analysis were baseline total femur BMD <1 g/cm2 (relative risk [RR], 3.86; 95% CI, 2.74, 4.22) and baseline lumbar BMD <1.2 g/cm2 (RR, 2.32; 95% CI, 1.53, 2.59). The probability of development of OP was 0.969 when both BMD measures were below the cutoff values compared to only 0.09 when the 2 parameters exceeded the cut points.2
The risk of fracture is estimated to be 5- to 23-times higher for individuals with a SCI compared to age-matched, unimpaired peers. The annual incidence of fracture is conservatively estimated to range from 2.2% to 2.8%, with the incidence increasing as more time elapses since the occurrence of the SCI. The annual incidence is approximately 1% for those with an injury sustained less than 10 years ago compared to 4.6% per year for an SCI that occurred more than 10 years ago. This is equivalent to a cumulative fracture rate of 40%, with most fractures affecting the knee, femur, tibia, or fibula. Fractures can occur during wheelchair transfers, as a result of falls or bumping into objects, or during low-impact activities such as the performance of range-of-motion activities or rolling in bed.1, 3 “Both individuals with paraplegia and tetraplegia have similar degree of bone mass loss, but, because individuals with paraplegia are more active, they incur more fractures” notes Cristina Sadowsky, MD, Clinical Director of the International Center for Spinal Cord Injury, Kennedy Krieger Institute, Baltimore, MD.
Fractures affecting individuals with SCI are associated with a high rate of complications including an extended length of hospital stay, development of pressure ulcers, increased pain, spasticity, non-union of the fracture, amputation, and increased mortality. Other common complications are respiratory illness, urinary tract infections, and delirium.1, 3 Importantly, individuals with SCI may be unaware of the acute fracture due to the absence of pain.1 W. Brent Edwards, PhD, Assistant Professor, Human Performance Laboratory, Faculty of Kinesiology, and Division of Physical Medicine and Rehabilitation at the University of Calgary, Canada comments, “The important thing to note is that all of these complications occur at a much younger age in people with SCI– people in the 20- to 50-year range.”
Interventions to protect bone health and reduce the risk of bone loss, OP, and fractures in patients with SCI are limited. Some antiresorptive medications are effective only for persons who do not sustain a neurologically motor complete SCI.1 While Dr. Edwards believes it is “too early to say for many bone-active agents, the lack of efficacy is most likely to do with the important neurogenic factors associated with SCI-related bone loss.”
“The lack of weight-bearing itself is sufficient to prevent antiresorptive agents from being efficacious in those with SCI who have the most severe forms of neurological motor impairments” adds William A. Bauman, MD, Director RR&D National Center of Excellence for the Medical Consequences of Spinal Cord Injury at the James J. Peters VA Medical Center, Bronx, NY and Professor of Medicine at the Icahn School of Medicine at Mount Sinai, New York.
As an alternative to pharmacologic interventions, attention has focused on mechanical loading and functional electrical stimulation (FES). Static mechanical loading following SCI does not appear to be effective in reducing the loss of BMD. Among individuals with chronic paralysis or an acute SCI, partial body weight-supported treadmill exercise also does not confer a protective effect on BMD.1 FES using surface electrodes that provoke the contraction of muscles does appear to have clinical benefit, particularly when administered at the time of the acute SCI. However, the effectiveness of FES is diminished for patients with chronic SCI and substantial, long-established bone loss, although bone mass increases to a lesser degree. Dr. Bauman points out that, “when one terminates FES, the beneficial effect on bone has been shown to be rapidly lost.” A combined approach integrating medical therapy with a mechanical intervention may offer the greatest benefit to patients with SCI, although this has not yet been demonstrated in clinical trials.1
Karen L. Troy, PhD, Department of Biomedical Engineering at Worcester Polytechnic Institute in Worcester, Massachusetts argues that “FES is a good solution for many patients, and should be more widely available. Unfortunately, there are many barriers to implementing this, such as time, cost, and the psychological adjustment of the recently-injured patient. I would personally argue that it is quite likely that significant advances in spinal regeneration and rehabilitation will be made over the next 20 years, and these may enable some individuals with SCI to regain some mobility, at least with assistance. We have already begun to see this with exoskeleton assisted walking devices that are available for home use. Can you imagine being told that you are not eligible to receive this assistive device because your bones are too weak?”
References
- 1. Bauman WA, Cardozo CP. Osteoporosis in individuals with spinal cord injury. PM R. 2015;7:188-201
- 2. Gifre L, Vidal J, Carrasco JL, et al. Risk factors for the development of osteoporosis after spinal cord injury. A 12-month follow-up study. Osteoporos Int. 2015;26:2273-80
- 3. Troy KL, Morse LR. Measurement of Bone: Diagnosis of SCI-induced osteoporosis and fracture risk prediction. Top Spinal Cord Inj Rehabil. 2015;21:267-74
By Carole Alison Chrvala, PhD
Reviewed by Clifton Jackness, MD, Assistant Professor, Hofstra Northwell School of Medicine, New York, NY
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