Osteoporosis After a Spinal Cord Injury Birgitte Hansen Clinic of Spinal Cord Injury Hornbæk - Denmark

Osteoporosis results from reduced bone mass disruption of the micro-architecture of bone, decreased bone strength increased risk of fracture.

A Spinal Cord Injury Has Increase in bone resorption Hormonal alternations Modification of body composition Wide-ranging physiological and pathological effects

1% - 46% incidence of lower extremity fractures in people who sustain an SCI

Risk Factors For Osteoporosis in SCI Individuals Completeness Low BMI (< 25 kg/m2) Age Gender (female) Age at injury ( < 18 years) Duration of injury

Bone Evaluation - DXA

What can we do?

Non pharmacological treatment Pharmacologic Therapy

Non pharmacological treatment MES (muscular electrical stimulation) FES cycle ergometry (functional electrical stimulation) Standing Walking Teach safe transferring skills

Passive standing do not maintain or improve BMD in the hip or knee region Kunkel et al (Arch Phys Med Rehabil) 1993 Needham-Shropshire et al. (Arch Phys Med Rehabil) 1997

FES cycle ergometry Conflicting results for bone parameters for six studies

MES –FES assisted training Belanger et al (Arch Phys Med Rehabil 2000) 14 men and women with SCI and 14 controls 5 days/week, 24 weeks Results BMD regained almost 30 % of lost bone mass compared to controls

Pharmacologic Therapy Calcium – just supplement Vitamin D – just supplement Calcitonin – optimal dosage and long-term effectiveness unclear Vitamin D analog (Etalpha®) – Increase in lower-limb BMD Bisphosphonates - reduction in bone loss

Vitamin D Analog Treatment

19 subjects had 1-α-D2 4 μg/day for 24 months (21 placebo) Leg BMD increased significantly from baseline in the treatment group at 12, 18 and 24 months. Both groups received calcium (1.3 g/d) and vitamin D (800 IU/d) Smoking prevents bone effect with 1-α-D2 - reason unclear

Conclusion – Vitamin D Analog Treatment of 1-α-D2 increased lower-limb BMD Current smokers had not this effect Long-term effect of continued 1-α-D2 therapy in persons with chronic SCI requires further investigation Bisphosphonates + 1-α-D2 or 1-α-D2 followed by bisphosphonates should be investigated 1-α-D2 + physical intervention may be considered

Bisphosphonates treatment First-generation Etidronate, clodronate Second-generation Pamidronate Third-generation Alendronate, ibandronate, risedronate, tiludronate and zolendronic acid

Treatment With Bisphosphonates Oral bisphosphonates must be Ingested on an empty stomach With 150-200 ml water Followed by sitting up for 1 hour prior to taking any other food or medication Side effects Joint pain Stomach upset/gastric ulcer

Treatment With Bisphosphonates II Intravenous bisphosphonates Available in daily, monthly, quarterly and yearly preparations Assured compliance Reduced relative risk of gastric ulcer Side effects Fever and muscle pain (flu-like symptoms) Low serum calcium

Clodronate P. Minaire et al. (J. Clin. Invest. 1981) Results 14 had clodronate (2 different doses), 7 placebo (17 males, 4 females) Started 17.6 days after injury. 3.5 months of treatment – total 6 months study Results No decrease in hip and knee region on bone mineral content in the treated groups Etidronate and Tiludronate have positive results for treatment within the 1 year of injury

Alendronate Y. Zehnder et al. (JBMR, 2004) Results 33 men had Aln + Ca, 32 men had Ca in 2 years 9.8 years since SCI Results BMD in distal and proximal tibia, and total hip remained stable in the Aln – Ca group and decreased in the Ca group

Future Prospects Large prospective longitudinal studies DXA methods to target areas Reducing the risk of falls Osteoprotegerin/RANKL system

Questions to be answered Who When How – and how long to treat?

Osteoporosis Research Centre, Hvidovre Hospital Ulla Pedersen Anne-Mette Rasmussen Solveig Petersen Jenni Teilmann Ole Helmer Sørensen Jens-Erik Bech Jensen Clinic For Spinal Cord Injury, Rigshospitalet Lisbeth Nielsen Fin Biering-Sørensen

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