Muscle and bone plasticity Muscle and bone plasticity after spinal cord injury:after spinal cord injury:

Review of adaptations to disuse and Review of adaptations to disuse and electrical muscle stimulationelectrical muscle stimulation

Group CGroup C

IntroductionIntroduction

The paralyzed musculoskeletal system retains a The paralyzed musculoskeletal system retains a remarkable degree of plasticity after spinal cord remarkable degree of plasticity after spinal cord injury (SCI)injury (SCI)

Muscles and bones show different changes and Muscles and bones show different changes and adaptations after the spinal cord has been adaptations after the spinal cord has been injured.injured.

Muscles atrophy and shift toward a fast-fatigable Muscles atrophy and shift toward a fast-fatigable phenotype arising from numerous changes in phenotype arising from numerous changes in histochemistry and numerous enzymes.histochemistry and numerous enzymes.

Bone mineral density (BMD) decreases as neurogenic Bone mineral density (BMD) decreases as neurogenic osteoporosis occurs in paralyzed limbs. The primary osteoporosis occurs in paralyzed limbs. The primary adaptations of bone to reduced use are demineralization adaptations of bone to reduced use are demineralization of epiphyses and thinning of the diaphyseal cortical wall.of epiphyses and thinning of the diaphyseal cortical wall.

However electrical stimulation of paralyzed muscle However electrical stimulation of paralyzed muscle markedly reduces deleterious post-SCI adaptations.markedly reduces deleterious post-SCI adaptations.

Physiological levels of electrically induced muscular Physiological levels of electrically induced muscular loading hold promise for preventing post-SCI bone mass loading hold promise for preventing post-SCI bone mass density declinedensity decline

Muscle adaptations to spinal cord Muscle adaptations to spinal cord injuryinjury

Muscle fibres contain slow and fast muscle fibres depending on their Muscle fibres contain slow and fast muscle fibres depending on their function.function.

Slow fibres (Type 1): Can perform prolonged work and are resistant Slow fibres (Type 1): Can perform prolonged work and are resistant to fatigue.to fatigue.

Fast fibres (Type 2): Can perform rapid action but fatigue quickly.Fast fibres (Type 2): Can perform rapid action but fatigue quickly. After SCI, muscles shift from slow to fast fibres.After SCI, muscles shift from slow to fast fibres. Histochemistry shows major changes in:-Histochemistry shows major changes in:-

• Myosin Heavy chain isoforms (MHC)• Myosin Heavy chain isoforms (MHC)• Sarcoplasmic reticulum Ca+2 ATPase isoforms (SERCA)• Sarcoplasmic reticulum Ca+2 ATPase isoforms (SERCA)

These changes are consistent with fast twitch muscle fibres. These changes are consistent with fast twitch muscle fibres.

The timeline of both these changes plus muscle atrophy The timeline of both these changes plus muscle atrophy vary but overall the shift supports the fast twitch fibres.vary but overall the shift supports the fast twitch fibres.

Atrophy may be faster than the transformation of the Atrophy may be faster than the transformation of the isoforms.isoforms.

Timeline:Timeline:• After 6 weeks lower limb muscles were 45% smaller • After 6 weeks lower limb muscles were 45% smaller than controls.than controls.• A complete transformation of Myosin Heavy Chains is • A complete transformation of Myosin Heavy Chains is complete by 17 months.complete by 17 months.• SERCA protein isoforms begin to adapt quickly and • SERCA protein isoforms begin to adapt quickly and transform gradually over time. transform gradually over time.

Muscle response to trainingMuscle response to training Electrical muscle stimulation to paralyzed muscles show Electrical muscle stimulation to paralyzed muscles show

the evidence of their increased use via hypertrophy and the evidence of their increased use via hypertrophy and improvements in fatigue resistance by increasing their improvements in fatigue resistance by increasing their oxidative capacity and glycolytic capacity.oxidative capacity and glycolytic capacity.

Low frequency(15 to 50Hz) repetitive stimulation is more Low frequency(15 to 50Hz) repetitive stimulation is more advantageous while high frequency (greater than 50) is advantageous while high frequency (greater than 50) is known to compromise with neuromuscular junction known to compromise with neuromuscular junction hence not recommendedhence not recommended

Load offers during electrically elicited contraction also Load offers during electrically elicited contraction also improve the training related changesimprove the training related changes

high resistance training shows more resistance against high resistance training shows more resistance against fatigue and metabolic adaptation by phosphocreatine fatigue and metabolic adaptation by phosphocreatine recovery than the low resistance training..recovery than the low resistance training..

Innervated and denervated musclesInnervated and denervated musclesMuscle transformationMuscle transformationFactors effecting hypertrophy of muscleFactors effecting hypertrophy of muscleMuscles load effects on bonesMuscles load effects on bones

Bone adaptations to SCIBone adaptations to SCI

As muscle is the primary deliverer of loads to the skeletal As muscle is the primary deliverer of loads to the skeletal system, the bones of paralyzed limbs lack an important system, the bones of paralyzed limbs lack an important stimulus for maintenance of bone densitystimulus for maintenance of bone density

When weight-bearing and muscular contraction diminish When weight-bearing and muscular contraction diminish or cease after SCI, the loss of mechanical loading yields or cease after SCI, the loss of mechanical loading yields an imbalance between osteoclastic and osteoblastic an imbalance between osteoclastic and osteoblastic activity.activity.

Bone resorption outpaces bone formation eventually Bone resorption outpaces bone formation eventually leading to neurogenic osteoporosisleading to neurogenic osteoporosis

Mechanism:Mechanism:

Within a few months after SCI, BMD starts to decline.Within a few months after SCI, BMD starts to decline.

Trabaculae in the epiphysis become fewer in number or Trabaculae in the epiphysis become fewer in number or may become perforated.may become perforated.

Disuse remodeling replaces trabecular lattice with fatty Disuse remodeling replaces trabecular lattice with fatty marrow.marrow.

Bone mass at the site of long diaphyses is lost via Bone mass at the site of long diaphyses is lost via thinning of the cortical wall, reducing the bone’s bending thinning of the cortical wall, reducing the bone’s bending stiffness.stiffness.

As a result overall bone strength decreases.As a result overall bone strength decreases.

Bone response to trainingBone response to training

BBiochemical stresses effect structure of skeletal iochemical stresses effect structure of skeletal systemsystem

loads applied to bone create stress.loads applied to bone create stress. change in length of bone is shearchange in length of bone is shear max. shear in young lamellar bone is 2.5% change max. shear in young lamellar bone is 2.5% change

in lengthin length remodeling on trabecular surface due to very low remodeling on trabecular surface due to very low

strain levels or disuse leads to demineralizationstrain levels or disuse leads to demineralization

AAnimal studies have shown adaptive capacity of bone to nimal studies have shown adaptive capacity of bone to mechanical loading at a high ratemechanical loading at a high rate

NNon-SCI animal models have pattern of bone loss on-SCI animal models have pattern of bone loss resembling that of human bone loss after SCI resembling that of human bone loss after SCI 

results showed potential usefulness of re-introduction of results showed potential usefulness of re-introduction of load after disuse-related BMD(bone mineral density) lossload after disuse-related BMD(bone mineral density) loss

IIn humans with SCI,DEXA(dual-energy X-ray n humans with SCI,DEXA(dual-energy X-ray absorptiometry)-based studies revealed no BMD effects absorptiometry)-based studies revealed no BMD effects with low level electrical stimulation and electrically with low level electrical stimulation and electrically stimulated cyclingstimulated cycling

Bloomfield and colleagues showed that unlike low Bloomfield and colleagues showed that unlike low intensity, high intensity work showed small BMD intensity, high intensity work showed small BMD increases at distal femur a trabecular boneincreases at distal femur a trabecular bone

Mohr and colleagues showed that SCI subjects who Mohr and colleagues showed that SCI subjects who increased their cycling work over 1 year, experienced increased their cycling work over 1 year, experienced 10% increase in proximal tibia, a trabecular bone10% increase in proximal tibia, a trabecular bone

33-dimensional densitometeric technique like peripheral -dimensional densitometeric technique like peripheral quantitative computed tomography p-QCT was used to quantitative computed tomography p-QCT was used to clarify the growth of trabecular bone from non clarify the growth of trabecular bone from non responding cortical boneresponding cortical bone

recent work on SCI subjects had 3 years of unilateral recent work on SCI subjects had 3 years of unilateral soleus stimulation.Trabecular BMD at distal tibia was soleus stimulation.Trabecular BMD at distal tibia was 31% higher in trained than in untrained limbs31% higher in trained than in untrained limbs

parts of the same limb without training experienced post-parts of the same limb without training experienced post-SCI demineralisation.SCI demineralisation.

Neural contributions to Neural contributions to musculoskeletal deteriorationmusculoskeletal deterioration

Bone has an extensive sympathetic sensory nerve Bone has an extensive sympathetic sensory nerve supply, particularly in metabolically active regions.supply, particularly in metabolically active regions.

These nerve fibers may sense local mechanical loads or These nerve fibers may sense local mechanical loads or may stimulate bone remodeling via neuropeptides, and may stimulate bone remodeling via neuropeptides, and because these nerves accompany intraosseous blood because these nerves accompany intraosseous blood vessels, they may also allow a communication between vessels, they may also allow a communication between the autonomic and skeletal systems.the autonomic and skeletal systems.

Although a link between autonomic disruption, Although a link between autonomic disruption, intramedullary venous stasis and osteoporosis has been intramedullary venous stasis and osteoporosis has been hypothesized, little is known about the underlying hypothesized, little is known about the underlying mechanism.mechanism.

ConclusionConclusion Rehabilitation specialists in the next decade will have an Rehabilitation specialists in the next decade will have an

important goal to minimize the deleterious metabolic important goal to minimize the deleterious metabolic chaos that results to the musculoskeletal system after chaos that results to the musculoskeletal system after SCISCI

New electrical stimulation technologies designed to New electrical stimulation technologies designed to capitalize on the extensive plasticity of paralyzed bones capitalize on the extensive plasticity of paralyzed bones and muscle must emerge and muscle must emerge

These technologies must be feasible so that an These technologies must be feasible so that an individual with SCI can comply with them and live a individual with SCI can comply with them and live a better life.better life.