Abstract
Individuals with spinal cord injury/disorder (SCI/D) are at high risk for developing secondary osteoporosis. Bone loss after neurologic injury is multifactorial and is dependent on the time from and extent of neurologic injury. Most bone loss occurs in the first year after complete motor paralysis, and fractures occur most commonly in the distal femur and proximal tibia (paraplegic fracture). The 2019 International Society for Clinical Densitometry Position Statement in SCI establishes that dual-energy X-ray absorptiometry (DXA) can be used to both diagnose osteoporosis and predict lower extremity fracture risk in individuals with SCI/D. Pharmacologic treatments used in primary osteoporosis have mixed results when used for SCI/D-related osteoporosis. Ambulation, standing, and electrical stimulation may be helpful at increasing bone mineral density (BMD) in individuals with SCI/D but do not necessarily correlate with fracture risk reduction. Clinicians caring for individuals with spinal cord–related paralysis must maintain a high index of suspicion for fragility fractures and consider referral for surgical evaluation and management.
Health Maintenance Checklist
DXA should be performed as soon as medically stable and repeated after at least 12 months of medical therapy and followed at 1- to 2-year intervals.
Maintain high index of suspicion for fragility fractures (the distal femur and proximal tibia are the most common sites of fractures).
Consider recommending physical modalities (ambulation, functional electrical stimulation, etc.) and pharmacologic management to decrease bone resorption and/or increase bone deposition.
Episodic Care Considerations
Consider referring long bone fractures for surgical consultation.
If low bone mass is diagnosed by DXA, consider optimizing metabolic parameters (calcium and vitamin D).
Case Report
A 25-year-old wheelchair-dependent man with motor complete paraplegia for the past 7 years presents with a right distal femur fracture occuring during a fall. He is otherwise healthy. He is concerned about the fracture and is inquiring what can be done to treat it and prevent another one. Clinician should refer to orthopedic surgeon for fracture stabilization assessment. It is recommended to obtain bone mineral density (BMD) assessment by dual-energy x-ray absorptiometry (DXA) on the contralateral side and/or intact anatomical sites and bone metabolic parameters in order to decide on a specific course of treatment. Assessment of other factors affecting bone metabolism (smoking, alcohol and caffeine consumption, calcium intake, vitamin D level, sun exposure, medications, exercise regimen) is also indicated. Educating the patient on risks of falling and subsequent fractures, use of caution during transfers, and stretching and other activities of daily living (ADLs) and mobility tasks, including regular wheelchair skills, is advised.
Background
In 2001, the National Institutes of Health Consensus Development Panel on Osteoporosis issued a consensus definition of osteoporosis: “Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture.”1 The diagnosis of osteoporosis can be made clinically, as related to occurrence of low-impact, pathologic fractures or through imaging, determining the bone mass using DXA.2 There is primary osteoporosis (related to estrogen deficiency and/or age) and secondary osteoporosis (caused by other diseases or medication)3 ; spinal cord injury/disorder (SCI/D)–related osteoporosis is part of the secondary group.
Bone Loss in SCI/D-Related Paralysis
Bone loss after neurologic injury is postulated to be multifactorial: severe immobilization and loss of weight loading related to paralysis,4,5 sensory and sympathetic denervation of the bone,6,7 loss of anabolic factors (ie, testosterone, growth hormone),8 presence of catabolic factors (systemic inflammation, administration of drugs like steroids at the time of injury),9 other factors locally influencing bone metabolism (ie, paracrine influences from atrophied muscles),10 and chronic administration of drugs known to negatively affect bone metabolism (antidepressants, anticonvulsivants, opioids, proton pump inhibitors, anticoagulants).11 Bone loss is dependent on time from and extent of neurologic injury, with most bone loss occurring in the first year after complete motor paralysis.12
SCI/D-related osteoporosis causes bone loss in different locations, thus influencing fracture location and BMD assessment. Primary osteoporosis-related fractures occur in the lumbar spine, hip, and forearm,13 while SCI/D-related fractures occur most frequently around the knee (distal femur, proximal tibia),14 increasing morbidity and mortality.15
Use of DXA in SCI/D-Related Paralysis
In able-bodied individuals, DXA of the lumbar spine and one hip is the gold standard for measurement of BMD and can be used to predict future fracture risk and assess response to pharmacological therapies. In SCI/D-related osteoporosis, total hip, distal femur, and proximal tibia bone density assessed in densitometry centers with knowledge in SCI/D should be used where normative data are available.16 Of importance, there are no population-based established reference values for knee bone DXA, thus, when possible, precision studies for the determination of least significant change (LSC) should be calculated using individuls with SCI.16 The lumbar spine BMD is usually normal or elevated in individuals with SCI/D, possibly secondary to increased osteoarthritic changes in that region.17 Sometimes, the lumbar spine site cannot be used for BMD assessment because of metallic artifacts from spinal stabilization. Measuring only one of the hips can lead to underdiagnosis of abnormally low bone mass,18 especially if there is a discrepancy between the legs in the extent of paralysis and/or muscle function.
DXA evaluation can yield two scores: Z-score, which compares BMD of an individual with age-matched, gender-matched, and ethnic-matched controls, and T-score, which compares BMD of an individual with reference values for peak bone mass, usually achieved between 20 and 30 years of age. When evaluating the bone mass of an individual older than 50 years of age, the T-score should be used to diagnose primary osteoporosis. According to World Health Organization, normal bone mass is characterized by a T-score of −1.0 SD or higher; T-score between −1.0 and −2.5 SD is indicative of osteopenia, and a T-score equal to or lower than −2.5 SD is indicative of osteoporosis. By convention, for individuals under 50 years of age, the Z-score is used to evaluate bone density. As the average age at injury for traumatic SCI is 43,19 the diagnosis of osteoporosis in patients with SCI is made only when they sustain a low impact fracture; otherwise, a diagnosis of “normal or low bone mass according to chronologic age” is made when the Z-score is −2.0 or under.20
Management of Bone Health in the Context of SCI/D-Related Paralysis
Bone health is ensured by ongoing and balanced bone resorption and deposition. The aim of osteoporosis treatment is to prevent ongoing bone loss and reduce the risk of fractures. In primary osteoporosis, this can be accomplished with several drug classes, including bisphosphonates (alendronate, ibandronate, risendronate, zolendronate), calcitonin, strontium ranelate, synthetic parathyroid hormone (teriparatide, abaloparatide), anti-RANKL human monoclonal antibody (denosumab), and anti-sclerostin human monoclonal antibody (romosozumab).
Secondary osteoporosis related to SCI/D is characterized by massive bone loss within the first years after the injury, compounded afterward by significant decrease in bone formation. There is evidence that bisphosphonates and anti-RANKL monoclonal antibody denosumab can mitigate bone loss in the lower limbs in individuals with SCI/D when they are administered early21,22 or even later after the onset of neurologic injury.23,24 The role of bisphosphonates administration on increasing bone mass at the knee (distal femur and proximal tibia), the area most susceptible to fractures in patients with SCI/D, is more controversial, with some studies showing no significant benefit25 and others showing increase in bone mass.26,27 Teriparatide, which increases osteoblastic activity (thus bone deposition), may have positive effect on increasing bone density of the spine, hip, and knee in individuals with SCI/D-related paralysis,28 but no studies utilized fracture occurrence as outcomes, thus efficacy in fracture prevention was not assessed.
The US Preventive Services Task Force concluded that there is insufficient evidence to assess the benefits and harms of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in able-bodied men and premenopausal women.29 Although individuals with SCI/D-related paralysis have been found to have low vitamin D level,30 there is no evidence that vitamin D supplementation reduces fracture incidence.
Studies that evaluated the effect of different physical modalities on bone mass in individuals with SCI/D31 suggest some benefit from standing and ambulation,32 functional electrical stimulation,33–35 and other physical modalities (ie, pulsed electromagnetic fields, low-intensity ultrasound).36 The 2019 ISCD position statement16 specifies there is no established threshold BMD value below which weight-bearing activities are absolutely contraindicated, and BMD and clinical risk factors should be used to assess fracture risk prior to engaging in weight-bearing activities. No correlation between exercise, modalities, and fracture rates has been established.37,38
The lack of substantial evidence that one intervention is effective and superior over another in fracture prevention24 presents a particular challenge in managing bone health in individuals with SCI/D-related paralysis. In the presence of significant morbidity (low bone mass and occurrence of low-impact fractures), the goal of clinical practice is to prevent bone loss in the immediate acute and subacute period after the injury and to preserve or restore bone mass in the chronic postinjury period. During the acute and subacute postinjury periods, this includes administration of bisphosphonates (weekly alendronate or every 6–12 months zoledronic acid infusion),39,40 optimization of metabolic parameters (vitamin D and calcium level), and early initiation of weight loading and other physical modalities through adequate rehabilitation. In the chronic postinjury period, measurement of bone turnover markers (i.e., C telopeptide as an indicator of bone resorption and osteocalcin, P1NP as indicators of bone formation) in order to assess the state of bone remodeling is helpful. Changes in these markers are associated with increased fracture risk independent of bone density and can be useful to guide osteoporosis management in high-risk patients.41
The 2019 ISCD Official Position16 clarifies that bone health follow-up using DXA should include evaluation of BMD at the total hip, distal femur, and proximal tibia, following a minimum of 12 months of therapy at 1- to 2-year intervals. To accurately track an individual’s bone changes over time, the DXA should be completed on the same testing unit, which has had analysis of its precision, as expressed by the least significant change (LSC) index, a marker of meaningful bone mass change.
Use of the Fracture Risk Assessment Tool (FRAX) is not appropriate for individuals with paralysis as this tool has not been validated in this population. Clinicians should use SCI/D-specific risk factors to identify individuals with high risk of fragility fractures.37,42
Clinicians caring for individuals with SCI/D must maintain a high index of suspicion for fragility fractures and refer patients for specialized care when long bone fractures occur. In the absence of pain, a fracture may be suspected on the basis of the presence of localized swelling, deformity, autonomic symptoms, and so on. Many fractures of osteoporotic bones can be treated with well-padded splints or bivalved circular casts for easy removal and frequent inspection of the skin in the sensory impaired limb. Surgical stabilization is commonly done, as fractures in this population are frequently complicated by non-union, development of heterotopic ossification, limb length discrepancy, increased likelihood for venous thromboembolic disease, spasticity and neuropathic pain, difficulties with seating and positioning in the wheelchair and overall, and across the board decrease in mobility and quality of life.43
Conclusion
The diagnosis and management of SCI/D-related low bone mass and its consequences differs significantly from primary osteoporosis. Heightened awareness and specialized knowledge on the part of health care providers is likely to enhance the quality of life in this group of individuals.
Key Take Home Points
Most bone loss occurs in the first year following neurologic injury and continues for years after.
Spinal cord injury–related fractures occur most commonly around the knee (distal femur/proximal tibia).
All adults with spinal cord injury resulting in permanent motor or sensory dysfunction should have a DXA (dual-energy x-ray absorptiometry) scan of the total hip, proximal tibia, and distal femur as soon as medically stable in order to diagnose osteoporosis, predict lower extremity fracture risk, and monitor response to therapy.
Acknowledgments
The authors report no conflicts of interest.