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

Paraplegia (1995) 33. 669-673 © 1995 International Medical Society of Paraplegia All righu reserved 0031.1758/95 $12.00 Bone metabolism in spinal cord injured individuals and in others who have prolonged immobilisation. A review D Uebelhartl.2, B Demiaux-Domenech3, M Rothl, A Chantrainel 1 Division of Physical Medicine and Rehabilitation, University Hospital, Geneva, Switzerland; 2 Department of Biochemistry, Rush Presbyterian St Luke's Medical Center, Chicago, Illinois, USA; 3 Division of Pathophysiology, University Hospital, Geneva, Switzerland 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. Keywords: bone metabolism; biochemical markers; densitometry; disuse osteoporosis; spinal cord injury; weightlessness; long-term bedrest; long term immobilisation Introduction Generic terms such as 'disuse' or 'immobilisation osteoporosis' have been used currently to describe the skeletal changes that occur in situations such as long-term bed rest, spaceflight or simulated weight lessness, loss of normal biomechanical function, and in neurological disorders associated with acute or chronic paralysis. The terminology used certainly does not reflect the aetiopathogenic factors involved in the occurrence of bone loss in any of these situations which are most likely to appear multifactorial in most of the examples. Nevertheless the loss of the normal bio mechanical stress associated with some degree of Correspondence: D Uebelhart, Department of Clinical Neuro sciences & Dermatology, Division of Physical Medicine & Reha bilitation, University Hospital - Beau Sejour, 1211 Geneve Switzerland This paper is dedicated to the memory of Pierre Minaire 14/ neurovascular changes due to modification of auto nomic nervous system activity have metabolic con sequences where bone tissue is one of the primary targets. This paper is aimed at making a short review of the major changes of bone metabolism in those with paralysis as seen in spinal cord injury patients, as compared to what is observed in healthy subjects submitted to a long duration of bedrest, or of micro gravity. The authors concentrated on the results of recent non-invasive techniques such as bone densi tometry and biochemical markers of bone and connect ive tissue metabolism to assess the effects of disuse. Bone metabolism in spinal cord injury patients In spinal cord injury patients (SCI), some alterations in bone metabolism can be reproducibly observed in cluding a rapid and intense bone loss occurring pre dominantly in the paralysed limbs, hypercalcemia and Bone metabolism in immobile individuals o Uebelhart et 01 670 hypercalciuria, and increased hydroxyproline excre tion. An invasive technique such as bone histomorpho metry has demonstrated a 33% decrease of the trabecu lar bone volume measured on iliac crest biopsies associated with increased bone resorption surfaces, a reduced bone formation rate1 and an increased bone marrow fat content.2 Using non-invasive techniques, such as dual-photon absorptiometry (DPA) it is pos sible to quantify bone loss more accurately. Using DPA, many studies have confirmed the rapid and important decrease of bone mass. Biering-Sorensen et al have observed in a 3 years prospective study a 50% decrease in bone mineral content in the paralysed limbs of SCI patients, mostly at the femoral neck and the proximal metaphysis of the tibia.3 Bone loss in the paralysed segments of the body has also been studied by transversal studies.4-7 More recently it has been demonstrated that total-body bone mass was also significantly decreased by -12% in paraplegic subjects6 and indeed all skeletal sites appeared to be concerned, with the exception of the skull.8 Recent data originat ing from our group confirm that bone mass is directly affected by paralysis, but muscle mass and fat mass are also affected. Using dual X-ray absorptiometry to assess whole-body composition in a prospective study including six young male SCI patients presenting with an acute complete traumatic paraplegia: bone mineral content (BMC) and density (BMD) of the lumbar spine and of the skull did not vary between the 1st (T1) and the 6th (T6) month after onset. In sharp contrast, in the lower limbs (LL) BMC decreased by 7.1% and BMD by 6.4% during the same time whilst there was a 4.8% increase in the upper limbs (UL) BMC. Whole-body BMC and BMD did not vary significantly between T1 and T6. LL-Lean body mass (LBM) decreased by 10.7% whereas it increased significantly by 19.6% in the UL during the same time. The total LBM decreased by 5% between T1 and T3, but no further loss could be measured up to T6. LL-Fat body mass (FBM) in creased by 39% but no change was seen in the UL during the time. The total FBM increased by 23% between T1 and T6 (D Uebelhart et aI, personal results). Bone mass homeostasis is difficult to assess precisely, but most authors agree that major bone loss occurs during the first 6 months after spinal cord inj ury, and stabilizes between 12-16 months at -2/3 of original bone mass, near the fracture threshold. Based upon av (...truncated)