The Pathophysiology, Identification and Management of Fracture Risk, Sublesional Osteoporosis and Fracture among Adults with Spinal Cord Injury

Background: The prevention of lower extremity fractures and fracture-related morbidity and mortality is a critical component of health services for adults living with chronic spinal cord injury (SCI). Methods: Established best practices and guideline recommendations are articulated in recent international consensus documents from the International Society of Clinical Densitometry, the Paralyzed Veterans of America Consortium for Spinal Cord Medicine and the Orthopedic Trauma Association. Results: This review is a synthesis of the aforementioned consensus documents, which highlight the pathophysiology of lower extremity bone mineral density (BMD) decline after acute SCI. The role and actions treating clinicians should take to screen, diagnose and initiate the appropriate treatment of established low bone mass/osteoporosis of the hip, distal femur or proximal tibia regions associated with moderate or high fracture risk or diagnose and manage a lower extremity fracture among adults with chronic SCI are articulated. Guidance regarding the prescription of dietary calcium, vitamin D supplements, rehabilitation interventions (passive standing, functional electrical stimulation (FES) or neuromuscular electrical stimulation (NMES)) to modify bone mass and/or anti-resorptive drug therapy (Alendronate, Denosumab, or Zoledronic Acid) is provided. In the event of lower extremity fracture, the need for timely orthopedic consultation for fracture diagnosis and interprofessional care following definitive fracture management to prevent health complications (venous thromboembolism, pressure injury, and autonomic dysreflexia) and rehabilitation interventions to return the individual to his/her pre-fracture functional abilities is emphasized. Conclusions: Interprofessional care teams should use recent consensus publications to drive sustained practice change to mitigate fracture incidence and fracture-related morbidity and mortality among adults with chronic SCI

Effect of functional sympathetic nervous system impairment of the liver and abdominal visceral adipose tissue on circulating triglyceride-rich lipoproteins.

Interruption of sympathetic innervation to the liver and visceral adipose tissue (VAT) in animal models has been reported to reduce VAT lipolysis and hepatic secretion of very low density lipoprotein (VLDL) and concentrations of triglyceride-rich lipoprotein particles. Whether functional impairment of sympathetic nervous system (SNS) innervation to tissues of the abdominal cavity reduce circulating concentrations of triglyceride (TG) and VLDL particles (VLDL-P) was tested in men with spinal cord injury (SCI).One hundred-three non-ambulatory men with SCI [55 subjects with neurologic injury at or proximal to the 4th thoracic vertebrae (↑T4); 48 subjects with SCI at or distal to the 5th thoracic vertebrae (↓T5)] and 53 able-bodied (AB) subjects were studied. Fasting blood samples were obtained for determination of TG, VLDL-P concentration by NMR spectroscopy, serum glucose by autoanalyzer, and plasma insulin by radioimmunoassay. VAT volume was determined by dual energy x-ray absorptiometry imaging with calculation by a validated proprietary software package.Significant group main effects for TG and VLDL-P were present; post-hoc tests revealed that serum TG concentrations were significantly higher in ↓T5 group compared to AB and ↑T4 groups [150±9 vs. 101±8 (p<0.01) and 112±8 mg/dl (p<0.05), respectively]. VLDL-P concentration was significantly elevated in ↓T5 group compared to AB and ↑T4 groups [74±4 vs. 58±4 (p<0.05) and 55±4 μmol/l (p<0.05)]. VAT volume was significantly higher in both SCI groups than in the AB group, and HOMA-IR was higher and approached significance in the SCI groups compared to the AB group. A linear relationship between triglyceride rich lipoproteins (i.e., TG or Large VLDL-P) and VAT volume or HOMA-IR was significant only in the ↓T5 group.Despite a similar VAT volume and insulin resistance in both SCI groups, the ↓T5 group had significantly higher serum TG and VLDL-P values than that observed in the ↑T4 and the AB control groups. Thus, level of injury is an important determinate of the concentration of circulating triglyceride rich lipoproteins, which may play a role in the genesis of cardiometabolic dysfunction

Bone Mineral Density Testing in Spinal Cord Injury: The 2019 ISCD Official Positions.

Spinal cord injury (SCI) causes rapid osteoporosis that is most severe below the level of injury. More than half of those with motor complete SCI will experience an osteoporotic fracture at some point following their injury, with most fractures occurring at the distal femur and proximal tibia. These fractures have devastating consequences, including delayed union or nonunion, cellulitis, skin breakdown, lower extremity amputation, and premature death. Maintaining skeletal integrity and preventing fractures is imperative following SCI to fully benefit from future advances in paralysis cure research and robotic-exoskeletons, brain computer interfaces and other evolving technologies. Clinical care has been previously limited by the lack of consensus derived guidelines or standards regarding dual-energy X-ray absorptiometry-based diagnosis of osteoporosis, fracture risk prediction, or monitoring response to therapies. The International Society of Clinical Densitometry convened a task force to establish Official Positions for bone density assessment by dual-energy X-ray absorptiometry in individuals with SCI of traumatic or nontraumatic etiology. This task force conducted a series of systematic reviews to guide the development of evidence-based position statements that were reviewed by an expert panel at the 2019 Position Development Conference in Kuala Lumpur, Malaysia. The resulting the International Society of Clinical Densitometry Official Positions are intended to inform clinical care and guide the diagnosis of osteoporosis as well as fracture risk management of osteoporosis following SCI

Characteristics of study cohorts.

<p>Characteristics of study cohorts.</p

Relationships between HOMA-IR and VAT volume and unadjusted TG concentration and number of large VLDL-P, respectively by group.

<p>In the ↓T5 group, the slope of the regression line significantly deviated from zero (p<0.05) in the respective relationships between unadjusted TG concentration and VAT volume (A) and HOMA-IR (B) and, for unadjusted Lg VLDL-P and VAT volume (C) and HOMA-IR (D), but not for the other groups. Similarly, the slope of the regression line for the ↓T5 group was significantly different (p<0.05) than the other groups for both unadjusted TG concentration models (A, B).</p> <p>Regression equations: </p><p></p><p>(A)</p><p>AB: TG = 89.81+0.01(VATvol)</p><p>↑T4: TG = 101.10+0.006(VATvol)</p><p>↓T5: TG = 107.02+0.25(VATvol); r²: 0.15, p<0.05</p><p></p><p>(B)</p><p>AB: TG = 86.33+13.31(HOMA-IR)</p><p>↑T4: TG = 98.14+7.01(HOMA-IR)</p><p>↓T5: TG = 118.62+19.92(HOMA-IR); r²: 0.10, p<0.05</p><p></p><p>(C)</p><p>AB: LgVLDL-P = 2.62+0.001(VATvol)</p><p>↑T4: LgVLDL-P = 3.15+0.001(VATvol)</p><p>↓T5: LgVLDL-P = 2.04+0.002(VATvol); r²: 0.22, p<0.05</p><p></p><p>(D)</p><p>AB: LgVLDL-P = 2.15+1.04(HOMA-IR)</p><p>↑T4: LgVLDL-P = 3.32+0.48(HOMA-IR)</p><p>↓T5: LgVLDL-P = 2.99+1.81(HOMA-IR); r²: 0.20, p<0.05</p><p></p><p></p><p></p> <p>AB: TG = 89.81+0.01(VATvol)</p> <p>↑T4: TG = 101.10+0.006(VATvol)</p> <p>↓T5: TG = 107.02+0.25(VATvol); r²: 0.15, p<0.05</p> <p>AB: TG = 86.33+13.31(HOMA-IR)</p> <p>↑T4: TG = 98.14+7.01(HOMA-IR)</p> <p>↓T5: TG = 118.62+19.92(HOMA-IR); r²: 0.10, p<0.05</p> <p>AB: LgVLDL-P = 2.62+0.001(VATvol)</p> <p>↑T4: LgVLDL-P = 3.15+0.001(VATvol)</p> <p>↓T5: LgVLDL-P = 2.04+0.002(VATvol); r²: 0.22, p<0.05</p> <p>AB: LgVLDL-P = 2.15+1.04(HOMA-IR)</p> <p>↑T4: LgVLDL-P = 3.32+0.48(HOMA-IR)</p> <p>↓T5: LgVLDL-P = 2.99+1.81(HOMA-IR); r²: 0.20, p<0.05</p

Unadjusted fasting blood and lipid profiles by group.

<p>Unadjusted fasting blood and lipid profiles by group.</p