Aging

Musculoskeletal System

The musculoskeletal (MSK) changes are the most obvious external signs of aging, as most people have some wear and tear on this system as they age (Aldwin & Gilmer 2004). Changes in the MSK system after long-term SCI may lead to upper extremity pain (Waters et al. 1993), reduced strength due to muscle atrophy (Giangregorio & McCartney 2006), and an increased risk for fractures (Lazo et al. 2001). Hence, the complications associated with a degenerating MSK system hold serious implications in terms of functionality for the person aging with SCI.

In terms of bone health, peak bone mass is achieved by the age of 30 in the general population and then declines, but the rate of decline is affected by a number of factors such as age, gender, and lifestyle (e.g., smoking). Although the risk for osteoporosis and fracture are greater among post-menopausal women over the age of 65 in the general community (Goddard & Kleerekoper 1998), there is evidence for increased risk in the SCI population (Ingram et al. 1989; Garland et al. 1992; Lazo et al. 2001). After sustaining a SCI, there are several reports of bone loss occurring in the early months following injury (Garland et al. 1992). These losses are regional; areas rich in trabecular bone are demineralized to the greatest degree, with the distal femur and proximal tibia bones being the most affected, followed by the pelvis and arms (Garland et al. 2001a). However, there is some evidence that there is a continual loss of bone mass with time since injury (Demirel et al. 1998; Bauman et al. 1999), which suggests that a steady state of lower extremity bone mineral homeostasis is not reached (Craven et al. 2014). Assuming that the rate of bone loss in the aging SCI-population is similar to that of the non-disabled population, it is likely that the degree of osteoporosis will be much more severe since they will have less skeletal mass at the onset of typical age-related declines in bone mass (Waters et al. 1993).

As a result of bone loss associated with SCI, there is an increased risk for fracture (Garland et al. 2001a; Craven et al. 2014). After SCI, the most common areas at risk for fracture include the distal femur and proximal tibia, and are consistent with site-specific decreases in bone mineral density around the knee (Craven et al. 2014). The majority of fragility fractures occur following transfers or activities that involve minimal or no trauma (Ragnarsson & Sell 1981). Individuals with SCI are more at risk for osteoporosis if they are older, and the time since injury is longer (Lazo et al. 2001). However, it is BMD, and not age per se, that is the significant predictor for risk of fracture (Lazo et al. 2001). Interestingly, the BMD of the spine is often maintained or actually increases (Garland et al. 2001a; Sabo et al. 2001).

Although BMD of the spine after SCI does not appear to be affected by aging, there are other age-related changes to the spine. With age the spine undergoes degeneration, which may cause deformity or nerve root compression that produces symptoms of pain radiating into the extremities, loss of sensation and/or motor function (Waters et al. 1993). Age-related degenerative changes in the spine may severely impact individuals with SCI whose functional capacities are already limited (Waters et al. 1993). Long-term SCI is associated with scoliosis and/orCharcot spine (progressive destruction of the spine and surrounding ligament leading to major spinal instability) (Sobel et al. 1985; Park et al. 1994; Krause 2000; Vogel et al. 2002; Abel et al. 2003). Age at injury, however, may also play a role as there is some lower level evidence that the odds of developing curvature of the spine is lower in persons who are older when injured (Krause 2000).

There are a variety of musculoskeletal changes associated with aging. In the general population, there is degeneration in the joints of the upper and lower extremities, and common sites include the shoulder, knee, and hip (Waters et al. 1993). As well, muscle atrophy is inevitable with age, although the rate of decline varies from person to person (Loeser & Delbono 1999). These age-related changes may lead to joint pain, stiffness, restricted range of motion, or trauma (i.e. fracture) that would not typically occur in a younger person. As a result, independence when performing daily activities may be compromised due to restricted activities of daily living, mobility. Lack of mobility may also affect temperature regulation (Aldwin & Gilmer 2004).

In addition to bone loss (see section 2.2.1), persons with SCI experience muscle atrophy (Giangregorio & McCartney 2006), especially among muscles that are denervated from complete SCI (Lam et al. 2006). In the lower extremities, muscle degeneration typically occurs around the knee in those who are capable of ambulation but have persistent gait abnormalities, which in turn may generate pathologic forces at the knee (Waters et al. 1993). Although persons who primarily utilize wheelchairs rarely develop clinically significant degenerative problems in the lower extremities, they are more likely to have problems in the upper extremities due to overuse of muscles needed to push their wheelchairs, to transfer, and perform weight-shift maneuvers to prevent pressure ulcers (Waters et al. 1993).

Upper extremity pain is common in persons with long-term SCI, and most frequently affects the shoulder and wrist (Sie et al. 1992; Thompson & Yakura 2001; Waters & Sie 2001), and typically increases with duration of injury (Sie et al. 1992; Ballinger et al. 2000; Waters & Sie 2001). The prevalence of shoulder pain in SCI ranges between 30-100% (Curtis et al. 1999) and is likely a consequence of increased physical demands and overuse (Nichols et al. 1979; Pentland & Twomey 1991). It is unclear, however, if these findings are independent of treatment era effects or are related to environmental changes in mobility technology, accessibility, and rehabilitation practices (Adkins 2004).

Losses in strength and diminished joint capacity along with joint degeneration due to overuse can negatively impact functional ability, which makes maintaining high levels of independence difficult. Since persons with SCI are operating at a near-maximum capacity but have a low reserve capacity, declines in functionality may occur prematurely (Thompson & Yakura 2001).

In this section, 12 longitudinal studies, 1 mixed longitudinal/cross-sectional study and 23 cross-sectional studies on the musculoskeletal system after SCI are reviewed.

Table 5. Musculoskeletal System

Author Year; Country Score Research Design Total Sample Size	Methods	Outcome
Coupaud et al. 2017; United Kingdom Prospective controlled trial Level 2 N_SCI=14 N_control=7	Population: 11 men (age range 17–59 years old; mean 35.7 ± 10.6) and 3 post-menopausal women (age range 56–58 years old; mean 56.7 ± 1.2 years) with motor-complete SCI (ranging from 6 months to 27 YPI) formed the study group. Early SCI group (<4 YPI): n=9 (6M, 3F); Established SCI (≥4 YPI): n=5 (5M, 0F). 6 uninjured men (age range 20–56 years old; 33.0 ± 12.7 years) and 1 post-menopausal woman (56 years old) formed the AB control group. Methodology: Individuals with chronic motor-complete SCI and age/gender matched AB control participants were recruited to determine whether the bone mineral density (BMD) along the tibia derived from multi slice peripheral Quantitative Computed Tomography (pQCT) would differ between individuals with SCI and healthy AB controls in both trabecular and cortical bone compartments. Outcome Measures: Trabecular and cortical BMD regions (volume, peak BMD, half-peak width, area under the curve) from the tibia.	Overall, SCI resulted in lower BMD at both trabecular and cortical regions of the tibia compared to the AB group. The peak volume of tibia model elements in the cortical BMD range in established SCI was almost half that of AB. There was no significant difference in peak trabecular volume between early and established SCI, but there was a trend for a gradual increase from AB to established SCI. In men, longer time since injury resulted in greater BMD differences when compared to AB, throughout the tibia. In post-menopausal women, differences in BMD between SCI and AB were greater in cortical bone than in trabecular bone. BMD distribution curves showed healthy double-peaks in AB participants: one trabecular peak and a larger cortical peak. In most participants with established SCI, trabecular peaks were exaggerated while the cortical peaks were barely discernible, with some individuals already exhibiting a diminishing cortical BMD peak at < 4 YPI.
Mulroy et al. 2015; USA Level 2 Longitudinal N = 201	Population: 201 participants with SCI present at 3-year follow up: mean age (y)=35.0+9.4. Majority of the sample size had lower paraplegia; Pain group (n=80), no pain group (n=121). Methodology: A 3-year longitudinal study was conducted, among people with paraplegia who used a manual wheelchair for at least 50% of their mobility to determine predictors of shoulder joint pain. Measurements were taken at baseline, 18 months, and at 3 years, self-reported daily transfer and raise frequency data were collected by phone every 6 weeks. Outcome Measures: Maximal shoulder torque, Wheelchair User’s Shoulder Pain Index, wheelchair propulsion (WCP).	80 participants (39.8%) developed shoulder pain at some point over the 3-year study period. Of those who developed shoulder pain, 55 developed shoulder pain at the 18-month follow-up, 18 had pain in the left shoulder only, 32 had right shoulder pain only, and 30 had pain in both. None of the WCP (average speed and distance) or other daily activity variables (frequency of car transfers, other transfers, raises, or weekly hours of sports participation) were a significant predictor of shoulder pain onset after controlling for time since SCI. Baseline maximal isometric torque in all of the major shoulder muscle groups was 10%-15% lower in participants who eventually developed shoulder pain than in those who remained pain-free Lower shoulder adduction torque was a significant predictor of shoulder pain development, explaining 7.5% of variance of shoulder pain onset.
Eriks-Hoogland et al. 2014; The Netherlands Level 2 Longitudinal N = 225	Population: 225 participants with SCI (74.7% Male); Mean age (y)= 40.7 (range 18-66); Type of injury: tetraplegia (n=91, 40.4%), motor complete (n=152, 67.6%). Presence of any shoulder pain (43.1%); presence of limitation in shoulder ROM > 10 degrees (35.6%). Methodology: Measurements for shoulder pain were taken at the time when a participant was able to sit four or more hours in the wheelchair (t1), 3 months later (t2), at discharge from inpatient rehabilitation (t3), and 1 and 5 years after inpatient rehabilitation (t4 and t5, respectively). Latent class growth mixture modeling was used to identifying the distinct shoulder pain trajectories. Outcome Measures: Shoulder pain, shoulder ROM, manual muscle strength (MMT), obesity, spasticity of upper elbow flexors/extensors	A prevalence of musculoskeletal shoulder pain in the total group was found to be 43% at start of active rehabilitation, 50% 3 months later, 40% at discharge, 34% 1 year after discharge, and 42% 5 years after discharge. Three distinct musculoskeletal shoulder pain trajectories in persons with acute SCI existed: a “High pain” trajectory (30%), a “Decrease of pain” trajectory (6%), and a “No or Low pain” trajectory (64%). The group with the “High pain” trajectory compared with the “Decrease of pain” trajectory showed to be more often obese, have a slightly higher MMT score, and suffer from more severe spasticity at t1. Significant predictors for the “High pain” trajectory (compared with the “No or Low pain” trajectory) were having tetraplegia (odds ratio (OR) = 3.2; P = 0.002) and having limited shoulder ROM (OR = 2.8; P = 0.007).
Verdijk et al. 2012; The Netherlands Prospective controlled trial Level 2 N SCI=8 N controls=16	Population: 8 young males with SCI (mean(SD) age: 32(4) yrs), 8 age-matched AB young males (mean (SD) age: 31(3) yrs), 8 AB older adult males (mean(SD) age: 75(2) yrs); SCI participants: mean (SD) DOI: 9(2) yrs; Level of injury: between C5-C6 and T9-T10. Methodology: Muscle biopsies were collected from all participants to determine skeletal muscle fibre type composition, fibre size, and satellite cell content. Outcome Measures: Muscle tissue characteristics; muscle fibre type, size, and composition; myonuclear content; satellite cell content.	Severe atrophy and a shift toward approximately 90% Type II muscle fibres were observed in muscle obtained from males with SCI. Muscle fibre size was substantially smaller in both the SCI (Types I and II fibres) and elderly participants (Type II fibres) when compared with the controls. Despite the young age, the SCI group had similar type II muscle fibre cross-sectional area as the elderly group. Satellite cell content was substantially lower in the wheelchair-dependent SCI participants in both the Types I and II muscle fibres when compared with the young controls. SCI group demonstrated severe muscle atrophy beyond what was observed in the elderly group.
Dionyssiotis et al. 2011; Greece Prospective controlled trial Level 2 N SCI=31 N controls=30	Population: 31 men with complete paraplegia (AIS A); >1.5 YPI; 16 in Subgroup A (T4-T7, mean (SD) age 32.88(15.6) yrs) and 15 in Subgroup B (T8-T12, mean (SD) age 39.47(13.81) yrs); 30 age-height-weight-gender matched AB controls, mean(SD) age 33.9(3.81) yrs. Methodology: Comparison of the influence of positive (spasticity, standing-therapeutic walking), and negative factors (duration of paralysis) on bone structures between groups using pQCT measurement. Outcome Measures: Total, trabecular and cortical bone mineral density (BMD), cortical thickness at distal tibial epiphysis and tibial diaphysis, Stress Strain Index at 14% (SSI2) and 38% (SSI3) of tibial diaphysis.	All BMD parameters were significantly reduced for individuals with paraplegia compared to the control group. Individuals with SCI who used standing frames or long brace orthoses had statistically higher BMD trabecular, BMD total, and cortical thickness compared to individuals with SCI who used wheelchairs. Duration of SCI was significantly related to trabecular bone loss and cortical thickness in both SCI groups.
Akbar et al. 2010; Germany Case-control Level 3 N SCI=100 N controls=100	Population: 100 participants with paraplegia (72M 28F); SCI level T2-L3; mean(SD) age 52(9) yrs, range 29-70 yrs; mean YPI 33.7, range 29-48 yrs; wheel chair dependent for minimum 30 yrs; BMI <40; no active shoulder infection; no previous upper extremity surgery; 100 age and gender matched AB controls. Methodology: Comparison shoulder function, pain and prevalence of rotator cuff tears between individuals with paraplegia with at least 30 years experience with using a wheelchair and an age and sex matched control group. Outcome Measures: MRI, shoulder function (Constant score), pain (visual analog scale).	Shoulder joint pathology in paraplegic patients is caused by over-use rather than being primarily age-related. Shoulder function was significantly worse in the group with paraplegia compared to the AB control group. Pain scores were signifcanlty worse in the group with paraplegia. The prevalence of rotator cuff tears was significantly higher (i.e., 10 x greater) in the group with paraplegia than age-matched controls.
Dudley-Javoroski & Shields 2010; USA Prospective controlled trial Level 2 N SCI=15 N=10	Population: 15 participants with SCI (14M 1F); age at SCI (range 18-49 yrs); 10 age- and stature- (femur length) matched AB controls (9M 1F). Methodology: Comparison of BMD of the femur metaphysis (12% of length from distal end) by using pQCT imaging over two yrs. Outcome Measures: Bone mineral density (BMD).	The BMD of individuals with SCI was 1 standard deviation below the control groups BMD at 1.5 years and 2 standard deviations below at 2 years. In the first two years after SCI, individuals with SCI lost an average of 1.7% of the initial BMD per month.
Rittweger et al. 2010; Germany Prospective controlled trial Level 2 N SCI=9 N controls=9	Population: 9 men with SCI (lesions between L1 and T5, 8 motor complete, 1 motor incomplete); mean YPI 21.4 (range 9-32 yrs); mean age 21.4 yrs (range 17-35 yrs); 9 age-height-weight matched AB controls. Methodology: Comparison of the total mineral bone content in the tibia of SCI participants and AB controls. Outcome Measures: Serial tomographic scans performed sequentially in steps of 5% of the tibia length from distal to proximal.	Individuals with SCI had lower total bone mineral content than their AB counterparts. Differences were more pronounced at the distal and proximal regions than at the shaft regions of the tibia.
Frotzler et al. 2008; Switzerland Longitudinal Level 2 N=39	Population: 39 participants with SCI; 28 paraplegic, 11 tetraplegic; ASIA A and B; mean(SD) age 42.0(13.4) yrs, range 21-64 yrs; mean(SD) YPI 12.0(10.8), range 0.9-34 yrs. Methodology: To evaluate changes in bone mineral density (BMD) of distal epiphyses and midshafts of femur, tibia. Outcome Measures: Bone measurements by pQCT in the radius of the non-dominant arm and the tibia and femur of the opposite leg at baseline, 15 mos, and 30 mos.	No significant difference in any measurements in the femur (77.9% of scans show no change, 12.3% show decrease, and 9.7% show increase) or the tibia (69.4% show no change, 19.0% show decrease, and 11.6% show increase). Changes in the radius bone were not related to changes in the tibia or the femur. Neither time post-injury nor age were significant covariates for the tibial and femoral bone parameters Data show that there is initially a large decrease in bone parameters post-injury but steadies after 3-8 yrs.
Kivimaki & Ahoniemi 2008; Finland Case-control Level 3 N SCI=120 N controls=103	Population: 120 people with SCI at least 3 months post-injury (54 paraplegic, 66 tetraplegic, age 18-65 yrs), and 103 AB control participants. Methodology: Comparison of shoulder structure and function Outcome Measures: Ultrasonography; on the acromioclavicular joint, the supraspinatus tendon, bicipitus longus tendon and the tendon sheath, posterior glenohumeral joint space; performance-corrected Wheelchair User’s Shoulder Pain Index (PC-WUSPI).	Osteophytes were noted in the shoulders of 14% of able-bodied participants, 22% of participants with paraplegia, and 26% of participants with tetraplegia (p<0.05). The mean (SD) thickness of the bicipital tendon sheath was 4.0 mm (0.5 mm) among able-bodied participants and 4.5 mm (1.4 mm) among participants with SCI (p<0.01). Effusion was noted in 6% of shoulders of participants who used no assistive device or only used sticks or a rollator. Participants using a manual or an electric wheelchair, the corresponding figures were 27 and 25% (p<0.01).
Amsters & Nitz 2006; Australia Case-control Level 3 N SCI=30 N controls=30	Population: 30 men with tetraplegia, divded into four groups (age > 50 yrs and YPI < 5 yrs; age < 40 yrs and YPI < 5yrs; age > 50 yrs and YPI > 15 yrs; age < 40 yrs and YPI > 15 yrs); age and gender matched AB controls. Methodology: Comparison of posture. Outcome Measures: Posture, through photography of bony landmarks.	All SCI groups had higher occurrence of thoracic kyphosis than AB controls. Regardless of age and duration of injury, people with SCI did not sit with greater pelvic tilt than AB controls.
de Bruin et al. 2005; Switzerland Longitudinal Level 2 N=10	Population: 10 participants with SCI (9M 1F); mean(SD) age 40.9(19.7) yrs, range 19-81 yrs at follow-up. Methodology: Comparison of trabecular and compact bone mineral density (BMD) of tibia and radius at 5 wks post-injury and at approx. 3.5 YPI. Outcome Measures: Trabecular and compact BMD.	Trabecular tibia and compact bone BMD decreased within 3.5 YPI. No changes in radius trabecular bone were observed. Patterns suggest no steady state of bone BMD following 3 YPI.
Giangregorio et al. 2005; Canada Cross-sectional with AB controls Level 3 N SCI=2 N controls=2	Population: Both females; Twin pair 1 (TP1) – mean age 32 yrs; mean YPI 7; C7 complete tetraplegia; Twin pair 2 (TP2) – mean age 47 yrs; mean YPI 20; T8 paraplegia. Methodology: Comparison of bone mineral density (BMD), bone geometry, and muscle cross-sectional area (CSA) with monozygotic twin. Outcome Measures: BMD, bone geometry, and muscle CSA.	TP1: For the twin with SCI, the BMD of hip, distal femur, proximal tibia, and spine were 59.5% 46.6%, 53.1%, and 93.3%, respectively, of AB control. TP2: For the twin with SCI, BMD of hip, distal femur, proximal tibia, and spine were 36.2%, 35.9%, 39.2%, and 62.2% respectively, of AB twin control.
Jensen et al. 2005; USA Longitudinal Level 2 N=147	Population: 147 participants with SCI (110M 37F); mean(SD) age at follow-up 48.8(13.0) yrs, range 21-88 yrs; mean(SD) YPI at follow-up 16.6(10.4), range 3.2-57.4 yrs. Methodology: Examine the change in the prevalence and intensity of pain over time. Outcome Measures: Brief Pain Inventory Interference scale; Bodily Pain scale; SF-36; Mental Health scale (range of 2-6 yrs between assessments).	There was increased prevalence of shoulder pain over the time period (2-6 years).
Slade et al. 2005; USA Cross-sectional with AB controls Level 3 N SCI=19 N controls=17	Population: 19 women with complete SCI; separated into pre-menopausal and post-menopausal groups. Mean(SD) age of premenopausal (< 30 yrs) 23.0(2.55) yrs; mean(SD) YPI 5.6(2.33), Mean(SD) age of premenopausal (>35 yrs) 42.6(4.66) yrs; mean(SD) YPI 12.2(8.14) yrs.Mean(SD) age of post-menopausal 54.5(7.7) yrs; mean(SD) YPI 14.17(11.9); 17 age and gender matched AB controls. Methodology: Comparison of the trabecular bone of the knee. Outcome Measures: Trabecular bone thickness, trabecular bone volume.	SCI group: trabecular bone was significantly lower compared to AB controls. SCI groups had fewer (-19 and -26% less) and thinner trabeculae (-6%) that were spaced further apart (40% and 62% more space between structures) resulting in less trabecular bone volume (-22% and 33%) compared to AB controls.
Eser et al. 2004; Switzerland Case-control Level 3 N SCI=89 N controls=21	Population: 89 men with SCI; mean(SD) age 41.5(14.2) yrs, range 10-65 yrs; mean(SD) YPI 29.3(12.5), range 2 mos-50 yrs. Age and gender matched AB control Methodology: Comparison of bone mineral density of distal epiphyses and midshafts of femur, tibia, and radius. Outcome Measures: BMD of distal epiphyses and midshafts of femur, tibia, and radius.	Group with SCI had lower BMD than the AB control group.
Garland et al. 2004; USA Longitudinal Level 2 N=6	Population: 6 participants (5M 1F) with complete paraplegia (1 with L1 incomplete paraplegia); mean(AD) age 24.4(3.9) yrs. Methodology: Bone mineral density (BMD) measured from proximal to distal sites assessed at 33.5 and 523 days post-injury. Outcome Measures: Dual-energy X-ray absorptiometry (DXA) and ultrasound (US).	BMD of os calcis significantly decreased by 38% (as measured by DEXA) and 48% (as measured by US). BMD of knee, distal femur, and proximal tibia significantly decreased by 24%, 27%, and 32% respectively.
Siddall et al. 2003; Australia Longitudinal Level 2 N=73	Population: 73 participants with SCI (60M 13F); mean age at baseline 40 yrs, range 21-81 yrs; mean time post-injury at baseline < 6 mos. Methodology: of pain at less than 1 YPI and at 5 YPI. Outcome Measures: Pain intensity via numeric scale; Psychological distress; Von Korff chronic pain disability to assess pain interference on daily activities; assessed at less than 1 YPI and again at 5 YPI.	Mean onset for musculoskeletal pain was at 1.3(1.7) yrs, with a high prevalence at 5 yrs with an initial decline in the first 6 months post-.
Vlychou et al. 2003; Greece Case-control Level 3 N SCI=57 N controls=92	Population: 57 participants with paraplegia (33M 24F); mean age 37.8 yrs, range 21-66 yrs; YPI range 6 mos-27 yrs; age and gender-matched AB controls. Methodology: Comparison of bone mineral density (BMD) of the proximal and distal forearm, the femoral neck, the greater trochanter, and Ward’s triangle. Outcome Measures: BMD of the proximal and distal forearm, the femoral neck, the greater trochanter, and Ward’s triangle.	Group with SCI had lower BMD of femoral neck, greater trochanter, and Ward’s triangle. Among males, 23.3% lower BMD in femoral neck, 22.5% lower BMD in greater trochanter, and 20.8% lower BMD in Ward’s triangle compared to AB controls. In females, the deficiencies were 24.1%, 24.3%, and 24.2% respectively.
Petrofsky & Laymon 2002; USA Case-control Level 3 N SCI=50 N controls=50	Population: 50 AB male controls and 50 men with paraplegia (T4 complete, 3-10 YPI), age range 20-65 yrs, age-, height-, and weight-matched. Methodology: Both groups were stratified according to age and compared. Outcome Measures: Strength, endurance, blood pressure and heart rate responses to fatiguing isometric exercise.	Handgrip strength was higher in participants with paraplegia than controls (avg 589 N vs. 463 N); quadriceps extension strength was higher in controls (avg 696 N vs. 190 N) with decreases with age in both groups. Leg endurance was lower in the group with paraplegia but handgrip endurance was similar in both groups with endurance increases with age in both groups. Resting BP increased with age in both groups. Magnitude of pressor response to exercise increased with age in both groups. HR remained constant with age in both groups in response to quadriceps contractions; decreased 50% between ages 20-60 yrs in both groups for handgrip exercise.
Garland et al. 2001b; USA Case-control Level 3 N SCI=31 N controls=17	Population: 31 women with complete SCI, mean(SD) age 43.9(19.7) yrs, mean(SD) YPI 16.9(7.7). 17 AB age-matched women, mean(SD) age 44.7(2.5) yrs. Methodology: Bone mineral density (BMD) measured from lumbar spine, hip, and knee. Outcome Measures: Dual-energy X-ray absorptiometry (DXA).	BMD of spine in women with SCI was maintained or significantly higher compared to age-matched controls. BMD of hips and knee in women with SCI was significantly lower compared to controls. Women with a complete SCI incur a rapid bone loss in the knee, resulting in a BMD that is approximately 40% to 45% of the AB population, and that this loss is greater than the loss found in the literature for males with comparable injuries.
Dauty et al. 2000; France Case-control Level 3 N SCI=31 N controls=31	Population: 31 men with SCI; mean(SD) age 36(12.3) yrs, range 18-60 yrs; mean YPI 6, range 6 mos-19 yrs; age and gender matched AB controls. Methodology: Comparison of supra- and sublesional bone mineral density (BMD) and bone mineral content (BMC), and of blood and urine samples that included phosphocalcic parameters with determination of urinary hydroxyproline and deoxypyridinoline. Outcome Measures: supra- and sublesional BMD and BMC, blood and urinary phosphate level, and urinary levels of calcium, hydroxyproline and deoxypyridinoline.	SCI group had a lower sublesional BMD of 41% compared to AB controls. This loss of mass is increased at the distal femur (-52%) and proximal tibia (-70%). SCI group had lower BMD at the femoral neck and at the trochanter (39%) compared to AB controls. Also had lower BMC in lower limb (48%) and pelvis (55%). Blood phosphate level and urinary phosphate level were increased in the group with SCI compared to AB controls. Urinary levels of calcium, hydroxyproline, and deoxypiridoline are increased in the group with SCI compared to AB controls.
de Bruin et al. 2000; Switzerland Longitudinal Level 2 N=12	Population: 12 men with SCI; mean(SD) age 32.4(9) yrs, range 23-50 yrs at follow-up. Methodology: Monitoring changes in structural and geometric properties of the tibia and cortical bone. Outcome Measures: Structual and geometric properties of the tibia and cortical bone, assessed at 5 weeks post-injury and again at approx. 2 YPI.	Trabecular and cortical bone, and geometric properties of tibia bone decreased within 2 YPI.
Frey-Rindova et al. 2000; Switzerland Longitudinal Level 2 N=29	Population: 29 participants with SCI (27M 2F); age range 19-57 yrs. Methodology: To evaluate changes in Trabecular and cortical bone mineral density (BMD). Outcome Measures: Trabecular and cortical BMD, evaluated at 1, 6, 12, and 24 months past injury.	Trabecular BMD of radius and ulna decreased in persons with tetraplegia at 6 months (radius 19% less; ulna 6% less), and at 12 months (radius 28% less; ulna 15% less) post- injury.
Kiratli et al. 2000; USA Cross-sectional with AB controls Level 3 N SCI=246 N controls=188	Population: 246 participants with SCI (239M 7F); age range 21-78 yrs; YPI range 0.1-51. Methodology: Comparison of bone mineral density (BMD) throughout the femur and geometric properties at the femoral midshaft. Outcome Measures: BMD in various femoral regions.	SCI group had lower BMD in all femoral regions (27%, 25%, and 43% for femoral neck, midshaft, and distal femur, respectively). Group with SCI had lower BMD in cortical area of femoral midshaft.
Bauman et al. 1999; USA Cross-sectional with AB control Level 3 N SCI=8 N controls=8	Population: Able-bodied (AB) twins of 8 men with complete paraplegia: mean(SD) ages 40.4(10) yrs, mean(SD) YPI 16(9). Methodology: Bone mineral content (BMC) and density (BMD) for total and regional skeletal bone mass. Outcome Measures: Dual-energy X-ray absorptiometry (DXA).	Compared to twin controls, persons with SCI had significantly lower BMC, with predominant sites being the legs and pelvis. Duration of SCI, not age was associated to degree of leg bone loss in twin with SCI.
Lal 1998; USA Longitudinal Level 2 N=53	Population: 53 participants with SCI (35M 18F); mean age 37 yrs, range 19-81 yrs at baseline. Methodology: Monitoring incidence of degenerative shoulder changes. Outcome Measures: Incidence of degenerative shoulder changes, accessed through X-ray at baseline and every 2 years after until 5-15 YPI.	72% of sample demonstrated radiological evidence of degenerative changes, but only 11% reported shoulder pain. Persons with increased age (> 30 yrs) had increased incidence of radiographic changes. There was a correlation between individuals with higher level of wheelchair activity (72%), higher age (92% above and 8% less than 30 years) and female gender (89% females versus 65% males) more prone to develop degenerative changes in the shoulders, particularly in the acromioclavicular joint. Incidence of degenerative shoulder changes may be higher in persons who are older than 30 years and are less than 10 YPI, suggesting that degenerative changes may occur earlier than previously thought in persons with SCI.
Szollar et al. 1998; USA N SCI=176 N controls=62	Population: 176 men with SCI; mean age 41.2 yrs, range 20-59 yrs; YPI range 0.8-34. Methodology: Comparison of bone mineral density (BMD), serum levels of calcium, calcitonin, biochemical markers of bone formation, and parathyroid hormone (PTH). Outcome Measures: BMD of the lumbar spine, femoral neck, Ward’s triangle, and the greater trochanter, serum levels of calcium, calcitonin, biochemical markers of bone formation, and parathyroid hormone (PTH).	Spine BMD remained stable above fracture threshold in the 20-39 yr. and in the 30-49 yr. age groups. In all groups, there was progressive decrease in BMD at proximal femur, and began 1-9 YPI. For the 20-39 yr. age group, this was significant for all three areas. For the 30-49 yr. age group, this progressed at a slower rate, reaching threshold at 10-19 YPI for all three areas. PTH levels remained below the reference range, with a slight gradual increase after 1 YPI. Results suggest parathyroid dysfunction- related osteoporosis.
Szollar et al. 1997a; USA Case-control Level 3 N SCI=135 N controls=69	Population: 135 participants with SCI, mean(SD) age 48.8(1.3) yrs, range 20-78 yrs. 69 AB individuals, mean(SD) age 51.1(1.7) yrs, range 24-76 yrs. Methodology: Both groups were stratified according to age and compared; SCI patients were grouped according to neurologic group within the various age categories. Outcome Measures: Bone mineral density (BMD) in the lumbar spine, femoral neck, Ward’s triangle, and the greater trochanter.	Lumbar spine BMD of the 40-59 yr old and the aged 60+ SCI patients were significantly higher than AB counterparts Femoral region BMD of the 20-39 yr old and 40-59 yr old patients were all significantly lower than AB counterparts Hip region BMD loss occurred starting at 1 YPI, plateaus at 19 YPI and then improves. Spine BMD in patients never decreased significantly and started increasing as YPI increasing. Femoral neck and Ward’s triangle BMD decreased after 1 YPI. After 19 YPI, slight increase in both regions.
Szollar et al. 1997b; USA Case-control Level 3 N SCI=263 N controls=92	Population: 263 men with SCI; mean(SD) age 48.8(1.3) yrs, range 20-78 yrs; YPI range 0.8-53. Age and gender matched AB controls. Methodology: Comparison of bone mineral density (BMD) of the lumbar spine, femoral neck, Ward’s triangle, and the greater trochanter with AB controls. Outcome Measures: BMD of the lumbar spine, femoral neck, Ward’s triangle.	Lumbar spine BMD was stable Lumbar spine BMD maintained in all SCI groups, regardless of age at injury or level of injury. Persons injured less than 1 yr. had comparable BMD to AB controls. Persons aged 20-39 yrs. old who were injured more than 1 YPI had lower BMD in the femoral region than AB matched controls and 20-39 yr olds injured less than 1 YPI.
Chow et al. 1996; UK Case-control Level 3 N SCI=31	Population: 31 participants with SCI (19M 12F); age range 19-60 yrs; mean(SD) YPI 5.87(10.21) yrs, range 5 wks-36 yrs; age and gender matched AB reference population. Methodology: Comparison of bone mineral density (BMD) of right heal, lumbar spine, and proximal femur region (femoral neck, Ward’s triangle, trochanteric and inter-trochanteric), and of bonestructure (stiffness). Outcome Measures: BMD of right heel, lumbar spine, and proximal femur region (femoral neck, Ward’s triangle, trochanteric and inter-trochanteric); bone structure.	After 1 YPI, BMD in femoral neck was lower in the group with SCI compared to AB reference population. Bone mineral density (BMD) at the femoral neck was significantly lower than the AB control group (p< 0.05). SOS and “stiffness’ correlated significantly with BMD at the lumbar spine, Ward’s triangle, the femoral neck, the greater trochanter and the intertrochanteric site (P < 0.05). A negative correlation was found between the ultrasonic properties at the calcaneus and BMD at the lumbar spine which is in contrast to the positive relationship in normal subjects.
Bauman et al. 1995; USA Case-control Level 3 N SCI=100 N controls=50	Population: 100 men with SCI, mean(SD) age 51(14) yrs; mean(SD) YPI 20(13), range 1-48 yrs. 50 age and gender matched controls. Methodology: Comparison of serum calcium (Ca), phosphorus (PO4), albumin, alkaline phosphatase (Alk P), and parathyroid hormone (PTH) with serum 25-hydroxyvitamin D [25(OH)D]. Outcome Measures: serum levels of calcium (Ca), phosphorus (PO4), albumin, alkaline phosphatase (Alk P), and parathyroid hormone (PTH) with serum 25-hydroxyvitamin D [25(OH)D].	Mean serum 25(OH) D was higher in the group with SCI compared to AB controls (61 ± 21 v 46 -+ 18 pg/mL, P < .0005). In these subgroups with depressed serum 25(OH)D levels, the mean value was significantly lower in those with SCI than in controls (8 ± 3 v 14 — 1 ng/mL, P < .0001).
Wilmet et al. 1995; Belgium Longitudinal Level 2 N SCI=31	Population: 31 participants with SCI (24M 7F) with T2 – L3 paraplegia, mean age 32.5 yrs, range 17.5-65.5 yrs. Methodology: Total body and regional bone mineral content (BMC) and soft-tissue composition assessed at 5, 10, 20, 30, 40, and 50 weeks post-injury. Outcome Measures: Dual-energy X-ray absorptiometry (DXA) and soft tissue phantom.	Rapid BMC loss in paralyzed areas of approx. 4% per month in trabecular bone and approx. 2% per month in areas with mainly compact bone. Lean muscle mass decreased during first months post-injury in the legs while fat content increased.
Pentland & Twomey 1994; Canada Cross-sectional with AB controls Level 3 N SCI=52 N controls=52	Population: 52 men with complete paraplegia (T2-L5, mean age 44 yrs, mean YPI 17) and 52 age- and activity level-matched AB males. Methodology: Bilateral upper limb physical functions were compared between the paraplegic and AB groups. Outcome Measures: Concentric isokinetic average torque for shoulder, elbow flexion/extension, shoulder adduction and eccentric shoulder adduction, grip strength, shoulder and elbow active ROM, upper limb pain.	AB had greater bilateral shoulder flexion and SCI greater bilateral elbow extension. Impairment and activity level were better predictors of strength in 9/14 muscles tested, whereas age was a better predictor in AB group. Shoulder pain related to time since injury, not age; pain experienced by majority of participants with paraplegia (58-60%).
Vaziri et al. 1994; USA Cross-sectional with AB controls Level 3 N SCI=40 N controls=14	Population: 40 men with SCI; age range 25-69 yrs; YPI range 3-50 yrs. Methodology: Comparison of serum levels of parathormone (PTH), calcitonin, vitamin D (calcitriol), 25 hydroxy (OH) vitamin D, 1,25 (OH)2, ionized calcium (Ca++), and phosphorous. Outcome Measures: serum levels of parathormone (PTH), calcitonin, vitamin D (calcitriol), 25 hydroxy (OH) vitamin D, 1,25 (OH)2, ionized calcium (Ca++), and phosphorous.	Plasma PTH was lower in the group with SCI compared to AB controls, despite equivalent concentrations of Ca++. Plasma calcitrol was lower in the group with SCI compared to AB controls, and lower in persons with tetraplegia vs. those with paraplegia.
Catz et al. 1992; Israel Longitudinal Level 2 N=9	Population: 9 C3-T11 patients; age at enrollment: mean 37.5 yrs, range 24-67 yrs; AB controls from another study. Methodology: Lumbar spine dimensions assessed twice over 10 yr interval. Outcome Measures: Lumbar anteroposterior (AP) radiographs.	The normal aging process, including the horizontal spreading of the lumbar vertebral bodies and narrowing of the lumbar spinal canal, is not accelerated by SCI.
Finsen et al. 1992; Norway Case-control Level 3 N SCI=19 N controls=19	Population: 19 men with SCI; median age at injury 20 yrs, range 15-64 yrs; median YPI 4, range 7 mos-33 yrs; age and gender matched AB controls. Methodology: Comparison of bone mineral density (BMD) of lower and upper extremities, and of biochemical and bone markers. Outcome Measures: BMD of lower and upper extremities and of biochemical and bone markers.	SCI group had a significant BMD decrease in the metaphysis (45%) and diaphysis (26%) of tibia, while a barely significant difference of distal forearm was detected. SCI group had lower levels of serum creatinine, and higher levels of alanine aminotransferase, serum phosphate, follicle stimulating hormone, and sex hormone binding globulin (SHGB). Total testosterone was equivalent but when divided by SHGB, higher in the group with SCI.
Garland et al. 1992; USA Longitudinal Level 2 N=45	Population: 45 men with complete SCI; mean(SD) age 28.1(0.78) yrs – 25; mean(SD) days post-injury 114.1(8.6). Methodology: Assessment of total bone mass (TBM) and bone mineral density (BMD) at different times post-injury. Outcome Measures: TBM and BMD assessed at 114.1(8.6) days post-injury and again at 468.9(21) days post-injury.	TBM of the pelvis and legs decreased between initial and follow-up assessment. BMD of the distal femur and proximal tibia decreased between initial and follow-up assessment.
Biering-Sorensen et al. 1990; Denmark Longitudinal Level 2 N SCI=8	Population: 8 participants (6M 2F) with complete paraplegia (1 with L1 incomplete paraplegia; mean(SD) age 24.4(3.9) yrs. Methodology: Bone mineral content (BMC) from lumbar spine, femoral neck and shaft, proximal tibia and distal forearm assessed at 43 days, and 5-13 up to 31-53 months post -injury. Outcome Measures: Dual photon absorptiometry (DPA).	Lumbar spine and distal forearm BMC did not change over time. BMC in lower extremities (femoral bone and proximal tibia) decreased over time.

Discussion

In general, the evidence supports the notion that the musculoskeletal system undergoes obvious external signs of premature aging except for a few areas. Many studies found that there was rapid bone loss, and particularly for the pelvis and lower limbs within the acute stage post-SCI (Garland et al. 1992; Biering-Sorensen et al. 1990; Wilmet et al. 1995; Dauty et al. 2000; de Bruin et al. 2000; Frey-Rindova et al. 2000; Garland et al. 2004; Frotzler et al. 2008, Dudley-Javoroski & Shields 2010; Dionyssiotis et al. 2011). Further, this loss may be greater for females with SCI (Garland et al. 2001b) and is evident in both bone mineral density (BMD; amount of matter per cubic centimeter of bones) and content (BMC; bone mass). Similarly, there are bone geometric changes (Finsen et al. 1992; de Bruin et al. 2000; Giangregorio et al. 2005) that occur, which may be independent of chronological age and YPI (Slade et al. 2005).

Some of the findings are mixed with regards to the duration of decline. One study found that bone mass continues to decline throughout the chronic phase (Finsen et al. 1992), whereas another study reporting a rapid loss with stabilization after approximately 2 years (Dudley-Javorski & Shields 2010). A cross-sectional study with AB controls (Eser et al. 2004) and a longitudinal analysis of the same cohort of persons with complete SCI (Frotzler et al. 2008) found that tibial and femoral bone geometry and density properties reach a new steady-state within 3-8 YPI, with the time frame depending on bone parameter and skeletal site.

The use of peripheral quantitative computed tomography (pQCT) is viewed as a superior approach for investigating changes in BMD and BMC compared to dual energy X-ray absorptiometry, DXA), but there are some unresolved issues with the use of this technology in people with SCI (Dudley-Javorski & Shields 2010). A mixed cross-sectional and longitudinal study by Dudley-Javorski & Shields (2010) who used two approaches for studying declines in BMD via pQCT found BMD values of their SCI subjects (n = 15) fell below the lowest range of control values (n = 10), suggesting that subjects lost an average of 1.7% BMD per month within the first two years post-SCI. However, their subjects (N=4) who were followed longitudinally starting at approximately 2 years demonstrated no BMD decline over time. There is a need to better understand anatomical variations related to bone adaptive processes in order to account for SCI-related bone losses (Rittweger et al. 2010). As such, further refinement into bone assessment are needed to help clarify some of the mixed findings noted in the literature.

There are also a number of other factors that contribute to bone loss post-SCI. For instance, endocrine changes may be contributing to the losses in bone density (Dauty et al. 2000; Szollar et al. 1998; Finsen et al. 1992; Vaziri et al. 1994; Bauman et al. 1995). It is thought that altered bone structure and microarchitecture due to SCI (de Bruin et al. 2000; Eser et al. 2004; Giangregorio et al. 2005; Kiratli et al. 2000; Slade et al. 2005; Frotzler et al. 2008) leads to impaired calcium and phosphate metabolism and the parathyroid hormone (PTH)-vitamin D axis (Finsen et al. 1992; Vaziri et al. 1994; Bauman et al. 1995; Szollar et al. 1998; Dauty et al. 2000). For instance, Bauman and colleagues (1995) noted that the reduction in the bioavailability of vitamin D in persons with SCI is similar to that found in AB elderly persons. These changes have been shown to contribute to premature onset of osteoporosis and increased risk for fracture in total and regional sites following SCI when compared to the AB population (Garland et al. 1992; Szollar et al. 1997a; Szollar et al. 1997b; Dauty et al. 2000; Kiratli et al. 2000; Garland et al. 2001b; Vlychou et al. 2003; Eser et al. 2004; Giangregorio et al. 2005; Frotzler et al. 2008, Dudley-Javoroski & Shields, 2010), which may be more related to YPI than chronological age (Bauman et al. 1999; Garland et al. 2001b).

Age of SCI onset, however, may be an influential factor on the extent of the decline in bone loss (Garland et al. 2001b; Kiratli et al. 2000; Szollar et al. 1997a). For instance, the findings by Szollar and colleagues (1997a) provide evidence that the BMD of persons with SCI are significantly lower than the AB population, but that YPI (i.e., older adults injured at a young age) may be more influential on BMD changes in specific areas (i.e. femoral and trochanter regions), although older males may not be as severely affected. Persons who were 60 years or older had comparable levels to their age-matched AB controls in their BMD whereas persons in the younger age categories had significant differences in their femoral regions at different intervals (Szollar et al. 1997a). For instance, younger adults with SCI (20-39 year olds) had significantly lower BMD at 1-5 YPI and at 10-19 YPI in the femoral regions of their neck and trochanter when compared to their AB controls, and the mid-age group (40-59 year olds) only had lower BMD at 10-19 YPI in the femoral neck and trochanter regions. These findings possibly allude to premature aging occurring at specific intervals post-injury, most notably in the first year, in the femoral region in younger persons with SCI, and are consistent with the other identified studies (Garland et al. 1992; Biering-Sorensen et al. 1990; de Bruin et al. 2005; Frey-Rindova et al. 2000; Wilmet et al. 1995; Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; de Bruin et al. 2000; Kiratli et al. 2000; Eser et al. 2004; Frotzler et al. 2008). It may be that age-related factors become less important on changes in bone mass when an individual reaches a certain chronological age threshold (i.e. 60 years). At this point, other factors (i.e. immobilization) affecting bone mass may become more prominent. In general,all of these changes provide additional support that premature aging is occurring.

Gender also is an influential factor on bone loss. Garland and colleagues (2001b) provide evidence that women with a complete SCI incur a rapid bone loss in the knee, resulting in a BMD that is approximately 40% to 45% of the AB population, and that this loss is greater than the loss seen in males with comparable injuries. Unlike the findings by Szollar and colleagues (1997a), the pattern of bone loss of the hip was linear regardless of the age at the time of injury. The findings by Bauman and colleagues (1999), which used a cross-sectional monozygotic twin design, also shows evidence that duration of injury may be more closely associated to bone loss than current age. Although lifestyle habits such as smoking and alcohol intake were examined and found not to be significant, the sample in Bauman et al. (1999) study was quite small, and relatively young.

As well, a study by Slade and colleagues (2005) which compared bone loss at the knee between AB and SCI women who were pre- and post-menopausal concluded that although age and estrogen effects could not be independently discerned, it was unloading (lack of weight bearing) that resulted in the deterioration of trabeculae that occurs early post-injury. Given that SCI is less common in women, more studies are needed to further our understanding of the interaction between gender, SCI, and aging plays on bone loss.

Interestingly, the lumbar spine BMD of persons with SCI appears to increase with age regardless of YPI. Szollar and colleagues (1997a) interpreted this finding as either being representative of the lumbar spine becoming the primary weight-bearing region or that neuropathic osetorarthropathy (i.e. spectrum of bone andjoint destructive processes associated with neurosensory deficit) may have caused diffused increased radiodensity of the spinal column. The finding that BMD and BMC of the spine remains unaffected or increases is consistent with several other of the identified studies (Biering-Sorensen et al. 1990; Dauty et al. 2000; Chow et al. 1996; Garland et al. 2001b; Szollar et al. 1997b; Szollar et al. 1998), and are complementary to the findings by Catz and colleagues (1992). Based on their findings, Catz et al. (1992) concluded that an SCI injury does not accelerate the aging process of the lumbar spine, and that it may even prevent some expected spinal bone changes since no significant differences were detected between their group with SCI and their AB matched control group. However, they noted that a limitation of their study was that 10 years might be too short a duration to detect any significant effects. As well, the sample size was small and consisted of a heterogeneous group of spinal cord etiologies (i.e. non-traumatic). Finally, one study (Amsters & Nitz 2006) found that postural changes, such as thoracic kyphosis, might also be independent of age and YPI.

With regard to the upper extremities, the musculoskeletal system appears to decline with YPI (Siddall et al. 2003; Jensen et al. 2005; Akbar et al. 2010), with the incidence of shoulder pain increasing over time. However, the role of chronological age may also be influential (Lal 1998; Kivimäki & Ahoniemi 2008). The incidence of degenerative shoulder changes (Lal 1998) may be higher in persons who are older than 30 years and are less than 10 YPI, suggesting that degenerative changes may occur earlier than previously thought in persons with SCI.

In addition to the lumbar spine, there are other areas of the musculoskeletal system that are not negatively affected by aging. For instance, handgrip strength may increase with YPI in males with paraplegia relative to AB controls (Petrofsky & Laymon 2002). This may be due to the use of manual wheelchairs, as well as to age-related changes in muscle fibre composition, and/or to a reduction in intramuscular pressure (Petrofsky & Laymon 2002). As well, older males with paraplegia (45 years and older) may have comparable levels of upper extremity strength to AB controls (Pentland & Twomey 1994).

Conclusion

There is Level 4 evidence from 9 longitudinal studies (Biering-Sorensen et al. 1990; Garland et al. 1992; Wilmet et al. 1995; de Bruin et al. 2000; Frey-Rindova et al. 2000; Garland et al. 2004; de Bruin et al. 2005; Frotzler et al. 2008, Dudley-Javorski & Shields 2010) and Level 5 evidence from 15 studies (Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; Szollar et al. 1998; Bauman et al. 1999; Dauty et al. 2000; Kiratli et al. 2000; Garland et al. 2001b; Vlychou et al. 2003; Eser et al. 2004; Giangregorio et al. 2005; Slade et al. 2005; Dudley-Javorski & Shields 2010; Rittweger et al. 2010; Dionyssiotis et al. 2011) that there is a rapid loss of bone in the hip and lower extremities following SCI.

There is Level 2 evidence (Frotzler et al. 2008) and Level 5 evidence (Eser et al. 2004) that tibial and femoral bone geometry and density properties reach a new steady-state within 3-8 year post injury, with the time frame depending on bone parameter and skeletal site.

There is Level 5 evidence from three studies (Szollar et al. 1997a; Szollar et al. 1998; Garland et al. 2001b) that older males and females with SCI may not experience as rapid of a decline in bone mass compared to AB controls.

There is Level 5 evidence from two studies (Bauman et al. 1999; Garland et al. 2001b) that year YPI may be more associated with bone loss after SCI than chronological age.

There is Level 5 evidence (Slade et al. 2005) that there are differences in bone geometric indices and in structural properties in the lower extremities of women with SCIcompared to the AB women.

There is Level 5 evidence from five studies (Finsen et al. 1992; Vaziri et al. 1994; Bauman et al. 1995; Szollar et al. 1998; Dauty et al. 2000) suggesting that there are impaired biochemical and bone markers in persons with SCI compared to AB controls that persons with SCI are at greater risk for fracture due to the premature development of osteoporosis.

There is Level 2 evidence from a longitudinal study with AB controls (Catz et al. 1992), Level 4 evidence from a longitudinal study (Biering-Sorensen et al. 1990), and Level 5 evidence from five studies (Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; Szollar et al. 1998; Garland et al. 2001b) that premature aging does not occur in the lumbar spine after SCI. The possibility that the lumbar spine becomes the primary weight-bearing region, along with immobilization, may serve to protect age-related bone loss changes to this region.

There is Level 5 evidence (Amsters & Nitz 2006) that persons with SCI, regardless of age or YPI, had increased thoracic kyphosis compared to AB controls.

There is Level 5 evidence from two studies (Pentland & Twomey 1994; Petrofsky & Laymon 2002) that decreased hand grip strength does not occur in men with complete paraplegia and that continual wheelchair use may retard this aging process.

There is Level 5 evidence (Pentland & Twomey 1994) that upper limb pain in males with complete paraplegia who use manual wheelchairs may be attributed to longer YPI and not to chronological age.

There is Level 2 evidence from two longitudinal studies (Siddall et al. 2003; Jensen et al. 2005) showing that the incidence of shoulder pain increases over time in persons with SCI.

There is Level 2 evidence from a longitudinal study (Lal 1998) and Level 5 evidence (Kivimäki et al. 2008) that highlights chronological age having an important influence on developing shoulder pain.

Premature aging may occur in the femoral and hip regions in persons with SCI. It may be that declines in bone mass occur rapidly following injury, and reach a new steady state within 3-8 years post-injury, depending on the bone parameter and skeletal site.

Older males and females (< 60 years) with SCI may not experience rapid declines in bone mass in certain regions when compared to able-bodied controls.

Duration of injury may be more associated with bone loss after SCI than chronological age.

Women with complete SCI may be at a greater risk for fracture at the knee compared to males with SCI and the able-bodied population.

Premature aging may not occur in the lumbar spine after SCI.

Upper limb pain in males with complete paraplegia may be attributed to longer durations of injury and not to the aging process.

The incidence of shoulder pain increases over time, and that age of onset may contribute to the development of pain. Adults with SCI (< 10 years post-injury) who were 30 years and older were more likely to report shoulder pain over time than those who were less than 30 years of age.

Premature aging may not occur in hand grip strength in men with complete paraplegia. Rather, continual wheelchair use may retard the aging process in relation to handgrip strength.

Regardless of age or years post-injury, persons with SCI may have increased thoracic kyphosis than the able-bodied population.

Persons with SCI may have reduced lung capacity compared to able-bodied controls, but this reduction is due to SCI and not aging.