Changes in Osteoprotegerin/RANKL System, Bone Mineral Density, and Bone Biochemicals Markers in Patients with Recent Spinal Cord Injury

Abstract

This study analyzed the temporal and regional variations in bone loss and explored bone cell activities via biochemical markers during an extended follow-up in patients with spinal cord injury (SCI). In parallel, the possible role of the osteoprotegerin (OPG)/RANKL system in disuse osteoporosis was investigated. Seven male patients with acute and complete SCI (31.3 +/- 9.5 years) and 12 able-bodied (AB) men (26.9 +/- 4.2 years) participated in the study. Measurements were performed 16, 24, 36, 48, and 71 weeks after injury. At week 16, marked calcium homeostasis disturbance and a concomitant increase in bone resorption markers were observed, reflecting an intense bone degradation process. Resorption activity decreased continuously with time. Contrasting with the great rise in the resorption markers, the bone formation markers showed little variation. During the period of investigation, a loss in bone mineral density (BMD) was demonstrated for the total body (-4.3%), pelvis (-15.7%) and lower limbs (-15.2%), whereas BMD did not change at the lumbar spine, upper limbs, or skull. At all stages, SCI patients had lower serum RANKL levels and higher serum OPG levels than did AB controls, but no significant variation with time was observed for either cytokine. These findings suggest that bone resorption persisted long after SCI and specifically affected BMD at sublesional sites. The marked modification of serum OPG/RANKL levels in SCI patients suggests that this system is affected, in disuse osteoporosis. However, the precise biologic role of the OPG/RANKL system in the bone tissue of SCI patients has yet to be determined.

Bone loss in spinal cord-injured patients: from physiopathology to therapy

“…Spinal cord injury (SCI) has wide-ranging psychological and pathological effects, these last including an increase in bone resorption, [1][2][3] hormonal alterations [4][5][6] and modification of body composition. 7,8 The annual incidence of SCI differs according to the source but ranges from approximately 28.5 to 40 cases per million population.…”

“…loss, 11,15,16 especially in young adults. 17 During the first months postinjury, demineralization occurs exclusively in the sublesional areas and predominantly in weightbearing skeletal sites such as the distal femur and proximal tibia, which are trabecular-rich sites, 3,11,15,18,19 while the diaphyseal areas of the femur and the tibia, which are cortical-rich sites, are relatively spared. 19 Using the dual energy X-ray absorptiometry (DEXA) technique, Wilmet et al 7 reported a decrease in bone mineral content (BMC) during the first year postinjury of about 4% per month in areas rich in trabecular bone and 2% per month in areas containing mainly cortical bone.…”

“…21 Paradoxically, at the lumbar spine, which is mainly constituted of trabecular bone, no reduction in BMD occurs whatever the lesion level or postinjury duration. 1,3,11,[16][17][18][22][23][24][25][26][27][28][29][30][31] This has been demonstrated to be due to continuous body weight-bearing during wheelchair use. 1,11,23,24 However, it should be kept in mind that in certain cases, BMD at the lumbar spine can be 'falsely increased' by neuropathic spondylopathy.…”

“…3 During the first months following injury, the releasing of the mineral phase modifies calcium homeostasis. 37,38 Hypercalcemia and hypercalciuria, [37][38][39][40] which lead to the development of renal calculi 41 and to alterations in the calciotropic hormonal profile, 2,3,38,[42][43][44] are the most commonly encountered abnormalities. Histomorphometric data demonstrated that the principal cause of bone loss is the increase in bone resorption as defined by an augmentation in eroded surfaces and of the number of osteoclasts.…”

Physiological effects of lower extremity functional electrical stimulation in early spinal cord injury: lack of efficacy to prevent bone loss

“…Although well studied, 7,[11][12][13] there is conflicting evidence about the efficacy of electrically evoked muscle activation in the stimulation of bone metabolism (bone formation and/or reduction of bone loss), and the clinical role of functional electrical stimulation (FES) in the treatment of osteoporosis resulting from neurological damage. The reason for this conflict may be that bone metabolic abnormalities may be time dependent [14][15][16] or as-yet-unexplained factors affect the osteogenic response to mechanical strain. Alternatively, as it is well known that exerciseinduced bone effects are mode and dose dependent, and the exercise modes or doses used and/or tolerated by the patient with SCI may have been subtherapeutic.…”