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Fracture Risk following SCI

The vast majority of current evidence supports the importance of addressing fracture risk after SCI since there is a higher incidence of fragility fractures in this population (Table 1). The majority of fragility fractures occur following transfers or activities that involve minimal or no trauma (Comarr et al. 1962; Ragnarsson & Sell; 1981; Freehafer 1995; Akhigbe et. al 2015) where the distal femur and proximal tibia (knee region) are most at risk.

Recent findings from review studies in veterans (n=12,162) with SCI have found that 82.6% of all fractures were at the tibia/fibula, femur or hip (Fig 1). Further, individuals with SCI were less likely to receive surgical intervention, than people without SCI, although those with SCI who have surgery did not have increased mortality or adverse event rates (Bishop et. al, 2013; Bethel et. al, 2015). Delayed fracture union is common after SCI (Grassner et al. 2017). Following a fracture there is a five-year increased risk of mortality (Pelletier et al. 2014; Carbone et al. 2014).

 

Figure 1. Many of the fractures that individuals with SCI sustain occur in the region of the metaphysis and epiphysis. Source: http://sci.washington.edu/info/forums/reports/osteoporosis.asp#dx

 

Risk factors for fragility fracture after SCI include:

  • Sex
  • Age at injury
  • Time Post-Injury
  • Type of impairment
  • Low BMI
  • Low knee region BMD, and
  • Use of anticonvulsants, heparin, or opioid analgesics.

Women are at greater risk compared to men (Vestergaard et al. 1998; Lazo et al. 2001; Nelson et al. 2003; Garland et al. 2004). Increasing age and longer TPI (Frisbie 1997; McKinley et al. 1999; Garland et al. 2004; Garland et al. 2005) increases fracture risk which rises significantly at 10 years post-injury. Further, people with paraplegia have more fractures (Frisbie 1997) and those with complete injuries have greater bone mass loss compared with those with incomplete injuries (Garland et al. 2004; Garland et al. 2005).

A number of concurrent medications a patient is taking can also decrease or substantially increase fracture risk. These include but are not limited to: heparin, benzodiazepines, anticonvulsants, proton pump inhibitors, selective serotonin reuptake inhibitors and opioid analgesics. In a large retrospective cohort study of men with chronic SCI (n=6969, ≥ 2 years post-injury), the use of thiazide-type diuretics was associated with a 25% reduction in the risk of lower extremity fragility fractures (Carbone et al. 2013c). In contrast, the use of heparin (HR 1.48, CI 1.20-1.83), opioid analgesics (HR 1.80, CI 1.57-2.06), or anticonvulsants (HR 1.35, CI 1.18-1.54), especially the benzodiazepine sub-class (HR 1.45, CI 1.27-1.65), was associated with an increased risk of lower extremity fragility fractures in men with chronic SCI (≥ 2 years post-injury) (Carbone et al. 2013a, 2013b). Men with chronic SCI are at a slightly increased risk of lower extremity fragility fractures when exposed to proton pump inhibitors (HR 1.08, CI 0.93-1.25), selective serotonin reuptake inhibitors (HR 1.05, CI 0.90-1.23), or thiazolidinediones (HR 1.04, CI 0.68-1.61) (Carbone et al. 2013a, 2013b). However, these drugs and a prior history of fragility fracture or a history of fracture in a parent are known risk factors for the development of osteoporosis in the general population, and should, therefore, be considered when assessing fracture risk in SCI patients.

Table 1: Fractures and Risk Factors for Fragility Fractures after SCI

First Author

Year

N

Age

Range in Years (Mean±SD)

FracturesRisk Factors
Comarr

1962

N = 1,363

Age – 19-58

109 post-SCI incident lower extremity fractures occurred among 81 out of 1363 participants with traumatic SCI (57% paraplegia, 75% complete). Most common fractures were distal femur (37%), proximal femur (11%)Motor complete SCIparaplegia
Ragnarsson

1981

Study 1

N = 578

Age = 4-77

 

Study 2

N = 3,027

Age = 13-77

33 lower extremity fractures occurred among 23 out of 578 participants (15 men and 8 women) with chronic SCI (78% paraplegia, 91% complete). Most common fractures were supracondylar fractures of femur (33%), femoral shaft (30%) and tibial shaft (18%)Motor complete SCI
(National SCI Data Research Centre); 52 lower extremity fractures occurred among 44 out of 3027 participants (37 men and 7 women) with chronic SCI (70% paraplegia, 64% complete). Most common fractures were ankle (24%, tibial shaft (20%) and femoral neck (17%)N/A
Frisbie

1997

N = 120

Age = 20-77

 

103 fractures (82% lower extremity) occurred among 40 out of 120 men with chronic SCI (91% traumatic, 30% paraplegia, 80% complete). Most common fracture sites were hip, femoral shaft, supracondylar femur, and tibia.

 

Fracture incidence per age group:

15 fractures/1000 participants years (20-39 years)

31 fractures/1000 participants years (40-59 years)

46 fractures/1000 participants years (60-79 years)

 

Ageing; with fracture incidence rising with age
Vestergaard

1998

N = 438

Age = 10-80

Overall fracture rate among 438 participants (309 men and 129 women) with SCI (94% traumatic, 55% paraplegia, 68% complete) was 2%/year. cumulative fracture incidence=21%

 

Women > men;

men with a family history of fracture;

TPI ≥3 years;

level of SCI (cervical lesions with more fractures)*

McKinley

1999

N = 20,804

population-based

all ages

20,804 participants over a 20-year timeframe

 

Total number of participants involved in study: 1yr post-SCI,

6,776; 2yrs post-SCI, 5,744; 5 years post-SCI, 4,100; 10yrs post-SCI, 2,399; 15yrs post-SCI, 1,285; 20yrs post-SCI, 500

Prevalence of lower extremity fractures in women

1% (5 years post-SCI)

2% (10 years post-SCI)

3% (15 years post-SCI)

6% (20 years post-SCI)

Women > men;

TPI

Prevalence of lower extremity fractures in men

1% (5 years post-SCI)

1% (10 years post-SCI)

2% (15 years post-SCI)

2% (20 years post-SCI)

Lazo

2001

N = 41

Age = 56±13

41 men with traumatic or Ischemic chronic SCI (57% paraplegia, 93% complete)

26 fractures (82% lower extremity) in 14 participants

Most common fracture site was above knee (35%)

Low femoral neck BMD

(OR = 2.1, 95% CI = 1.27-3.43; per t-score decrement)

Nelson

2003

N = 23

Age = 39-85

23 participants (22 men and 1 woman) with SCI (44% paraplegia) over 10 years (2.7% of the group). 31 fall-related fractures (97% lower extremity.  Most common fracture sites were tibia/fibula (55%) and femoral fractures (35%)Falls among those age 39-59 years
Morse 2009b

N = 315

Age = 55.0±14.4

39 fractures occurred among 30 men with SCI (50% paraplegia, 83% motor complete) during the first-year post-injury. Most common fracture sites were tibia/fibula (47.5%), distal femoral metaphysis (20%) and proximal femur (15%)Motor complete SCI; post-injury alcohol consumption > 5 servings*/day
Garland

2004

N = 152

Age = 20-71

9 out of 152 participants with post-SCI fractures (130 men and 22 women) with SCI (54% paraplegia, 67% motor complete). TPI: 12.9 ± 9.3 (range: 1.1 to 44.4) years.Motor complete SCI; increasing age;

low BMI

Zehnder

2004a

N = 98

Age = 18-60

39 fractures occurred among 15 paraplegic men with traumatic motor complete SCI. Overall fracture incidence was 2%/year.TPI strata;

1%/year < 1-year post-SCI

1%/year 1-9 years post-SCI

3%/year 10-19 years post-SCI

5%/year (20-29 years post-SCI)

Low knee region BMD;

 

Eser

2005

N = 99

Age = 19-83

21 out of 99 participants (89 men and 10 women) with traumatic motor complete SCI (72% paraplegia) with lower extremity fracturesTPI;

trabecular vBMD less than:

114g/cm3 distal femur 4% site;

72g/cm3 distal tibia 4% site;

Garland

2005

N = 168

Age = 26-52

27 of 168 participants with chronic SCI (61% complete) with post-injury lower extremity fractureLow BMD <25kg/m2;

increasing age;

low BMI;

Carbone

2013a, 2013b

N = 7,447

Age = 58±13

892 out of 7447 men with chronic traumatic SCI (56% paraplegia, 37% complete) had incident lower extremity fragility fractures over 5 years (12% of the cohort)motor complete SCI;

use of anticonvulsants;(use of benzodiazepine or use of multiple anticonvulsants),

heparin use,

opioid analgesia use 28mg of morphine equivalent

Tan et. al

2014

N = 27

Age = 21 – 64

27 men with chronic traumatic SCI

(70% paraplegia, 82% complete)

6/27 men with post-SCI osteoporotic fractures

Higher level of adiponectin among wheelchair users

 

Range of values 5657 ± 3003 (wheelchair users with history of fractures)

 

Akhigbe et. al

2015

N = 140

Age = 56.5±12

140 participants (137 men, 2 women, and 1 unknown) with chronic traumatic SCI (67% paraplegia, 51% complete) with 155 incident lower extremity fractures. Common fracture sites were tibia/fibula (54%) and femur (33%)Transfers account for 1/3 of fractures
Bethel et. al 2016

N = 22,516

Age = 55±13

3365 participants (3,246 men and 119 women) with chronic SCI and incident fractures (66% traumatic, 44% non-traumatic, 38% with paraplegia, 42% motor complete) A majority ((80%) were lower extremity fractures; tibia/fibula (26%), femur (18%), and the hip (13%)White race;

Traumatic etiology of SCI; paraplegia;

Motor complete SCI;

TPI;

Use of anticonvulsants,

Use of opioids

Use of benzodiazepines;

History of prevalent fractures; higher Charlson Comorbidity Index score;

Women aged ≥ 50 years

Fracture thresholds are values below which fragility fractures begin to occur, whereas fracture breakpoints are values below which the majority of fractures occur (Garland et al. 2005). Knee region areal BMD (aBMD) and volumetric (vBMD) thresholds for fracture and breakpoint have been identified (Mazess 1990; Eser et al. 2005; Garland et al. 2005). BMD thresholds are described on Table 2.

Table 2: BMD thresholds for fracture and fracture breakpoint

NameValueDefinition
Fracture threshold≤ 0.78 g/cm2 (aBMD)

< 114 mg/cm3 (vBMD-femur)

< 72 mg/cm3 (vBMD-tibia)

Knee region BMD values below

which fragility fractures occur

Fracture breakpoint< 0.49 g/cm2 (aBMD)Knee region BMD values

at which the majority

of fragility fractures occur

BMD = bone mineral density; aBMD = areal BMD; vBMD = volumetric BMD.

 

Reproduced from Craven BC, Robertson LA, McGillivray CF, Adachi JD (page 7).1 © 2009

Thomas Land Publishers, Inc. www.thomasland.com. Reprinted with permission.

 

Fragility fractures, especially around the knee, are common in people with SCI.

 

We recommend documenting your patient’s fracture risk by completing the risk factor profile checklist (Craven et al. 2008; Craven et al. 2009). We propose that the presence of ≥ 3 risk factors implies a moderate fracture risk, and ≥ 5 risk factors implies a high fracture risk (Table 3).

Table 3: Risk Factors for Lower Extremity Fragility Fracture after SCI

YesRisk Factors
Age at Injury < 16 years
Alcohol Intake > 5 servings/day
Body Mass Index < 19
Duration of SCI ≥ 10 years
Woman
Motor Complete (AIS A-B)
Paraplegia
Family history of fracture in men
Anticonvulsant use (i.e., Tegretol, Depakote Gabapentin – Neurontin)
Spasticity Medication
Opioid analgesia use (≥28 mg morphine for 3 months)
Prior fragility fracture**
SSRI
PPI
Knee region BMD below the fracture threshold**
**The big 2**