Bone metabolism in spinal cord injured individuals and in others who have prolonged immobilisation. A review

Abstract

Immobilisation or disuse is a condition known to be associated with a decrease in bone mass, osteopenia and in some people leading to osteoporosis with an increased risk of fractures. In this condition, previous histomorphometric and biochemical reports have shown an uncoupling between bone formation and resorption, but the exact sequence of the events resulting in bone loss is still not fully understood. In spinal cord injury for instance, the main finding soon after the onset is decreased osteoblastic activity associated with a dramatic increase in bone degradation. The overall consequence of these metabolic events is the development of a rapid and severe osteoporosis only observed in the paralysed part of the body associated with the loss of biomechanical strength and the biosynthesis of a structurally modified matrix which is unable to sustain normal mechanical stress. This situation dramatically increases the risk of fractures. The same uncoupling phenomenon has been described in healthy individuals who have been submitted to long duration bedrest and also in astronauts during spaceflight; but the timing, intensity and the metabolic subset may be different as these people do recover after cessation of the disuse period, which does not occur in paralysed patients. As new accurate and sensitive non-invasive techniques have become available recently to assess bone and connective tissue metabolism, more information is now available regarding bone loss in paralysed and/or immobilised individuals. These techniques should be definitely helpful in orientating new therapeutic trials with drugs and/or procedures intended to correct the musculoskeletal deleterious effects of disuse. This paper is therefore aimed at a review of bone metabolism in those with a severe spinal cord injury, or with a long duration of bedrest, or with loss of biomechanical function, or with actual or simulated spaceflight, in all instances using non-invasive techniques.

Osteoporosis after spinal cord injury

“…1 ± 4 Most authors agree that major bone loss occurs during the ®rst 6 months after SCI and stabilises between 12 ± 16 months at two thirds of the original bone mass. 2 Some investigators suggest that immediately after SCI the balance between bone resorption and bone formation tips in favour of resorption. 5,6 The loss of the normal biomechanical stress associated with some degree of neurovascular changes due to autonomic nervous system activity have metabolic consequences where bone tissue is one of the primary targets.…”

“…5,6 The loss of the normal biomechanical stress associated with some degree of neurovascular changes due to autonomic nervous system activity have metabolic consequences where bone tissue is one of the primary targets. 2 The purpose of this study was to evaluate bone mineral density (BMD) in both the upper and lower limbs with spinal cord injury sustained for various lengths of time and to correlate BMD to the level of the spinal cord lesion, time from injury, spasticity and serum calcium, phosphorus and alkaline phosphatase levels.…”

Histomorphometric and Densitometric Changes in the Femora of Spinal Cord Transected Mice

“…On the other hand, growing evidence suggests that several factors, other than mechanical unloading per se, can influence the sets of cellular and molecular mechanisms underlying disuse-related bone loss (Uebelhart et al, 1995). For instance, in the case of disuse induced by sciatic nerve lesion in rats, bone tissue loss was found to be partly caused by a disruption of bone marrow innervation (neurogenic; Zeng et al, 1996;Kingery et al, 2003).…”

The role of androgens or growth factors in the bone resorption process in recent spinal cord injured patients: a cross-sectional study

“…33 In castrated patients 12 and in men with acquired hypogonadism, 33,34 a progressive loss of BMD in the lumbar spine has been observed, while in patients with SCI this specific bone site was not affected. 6,9,33 Our data suggest that the low TT level in the patients with SCI was not the major factor affecting the early bone loss, but it might have been an aggravating factor. The absence of published reports of vertebral fractures in these patients lends support to our findings.…”

“…8 However, this decrease alone cannot explain the difference in bone loss magnitude observed between patients with SCI and able-bodied subjects (AB) undergoing prolonged intervals of bed rest. 9 Other nonmechanical factors related to neurological lesion that may affect bone integrity have been proposed such as the vasomotor paralysis that slows intraosseous circulation 10 or the modification in the body blood volume distribution. 11 Moreover, various hormonal abnormalities -and, in particular, the androgen and growth hormone (GH) deficiency known to be implicated in bone loss and bone turnover alteration in AB men 12,13 -have been highlighted in chronic SCI patients.…”