1. Alternative Site Testing Heidi H. Kecskemethy, RD, CSP, CBDT Biomedical Research & Medical Imaging Departments

2. No disclosures to report

3. Overview  The Basics  What are Alternative Sites ?  Recommended Body Sites to Measure  Alternative Sites  Candidates  Case Study  Conclusion

4. Equipment – Measuring Bone Density  DXA Whole Body, PA & Lateral Spine, Proximal Femur, Forearm, Lateral Distal Femur, Hand  USCalcaneus, Forearm, Tibia  pQCT Forearm, Tibia  QCTSpine, Other Sites  MRISpine, Femur, Other Sites Each of these technologies have standard measurement sites  Varies by machine Normative values may or may not be available

5. What is Alternative Site Testing ?  “Creative Imaging”  Acquiring DXA at body sites other than those typically recommended  Applying the use of DXA in non-standard ways –Innovation (e.g. hemiscans, subregions) –Patient as own control in serial scans –Serial scans with no normative values

6. ISCD Recommended Body Sites to Measure  Differs for Adults vs. Children  2013 ISCD Official Positions – Adult and Pediatric Recommended Body Sites to Measure by DXA AdultPediatric Lumbar Spine (PA)Total Body Less Head Proximal FemurLumbar Spine (PA) Forearm (if unable to measure hip and/or spine, hyperparathyroidism, obesity)

7. Adult Alternative Sites  Forearm DXA Recommended and Alternative Sites WHOLE BODY SUBTOTAL WHOLE BODY (TBLH) LUMBAR SPINE HIP FOREARM LATERAL DISTAL FEMUR AdultPediatric

8. Alternative Sites Forearm Proximal Femur (pediatrics) Lateral Distal Femur

9. Alternative Sites - Forearm Measures distal radius and ulna Is a scan option on machines, with analysis protocols and norms Is a recommended site for adults in certain circumstances (official positions): –unable to obtain hip and/or PA spine –patient has hyperparathroidism –patient exceeds weight limit of table

10. In Pediatrics  Useful if patient exceeds weight limit of machine  Useful if other sites not obtainable  Utility has been shown to monitor site-specific change  Correlated with strength indices obtained from peripheral computed tomography (Dowthwaite, et al. JBMR 2011)  Norms are available Alternative Sites - Forearm

11. 11 Drawbacks  Normative data for Hologic machines only  Positioning can be challenging – reach, contractures  Poorest precision of all measurement sites (Shepherd, at al. JBMR 2011) Image source - Hologic Alternative Sites – Forearm (Pediatrics)

12. Alternative Sites: Proximal Femur (Pediatrics) Prior to pubescence, hip is undergoing ossification and mineralization Can lead to errors: - bone detection - ROI placement - poor reproducibility Boy 6 years Useable in skeletally mature children (post puberty) Normative data available on machines for children 3 – 20 years Girl 17 years

13. 13 Normative Data – Hip and Forearm  The Bone Mineral Density in Childhood Study (BMDCS) has published reference data on both hip and forearm scans http://www.bmdcspublic.com http://www.bmdcspublic.com  Normative data for the forearm and hip scans available on certain DXA machines – source of data and age ranges may vary by manufacturer

14. 14 Alternate Sites: Lateral Distal Femur (LDF) First developed in early 1990s by pediatric radiologist (Harcke) and pediatric orthopedic surgeon (Henderson) Measures site most commonly fractured in non-weight bearing children Increasingly used in pediatric facilities around the world

15. Developed because children with neuromuscular involvement frequently have joint contractures, non-removable indwelling artifacts (tubes, pumps, metallic hardware), and movement disorders Alternate Sites: Lateral Distal Femur (LDF)

16.  In children with physical disabilities, no clear link between LS BMD and fracture (Henderson, et al. Dev Med Child Neurol 1997; Henderson, et al. JBMR 2010)  Distal femur is most common site of fx in non-ambulatory children; 60 – 70% of fractures occurring in femur (Henderson, et al. Pediatrics 2002; Bachrach S, et al. Dev Med Child Neurol 2008)  Children who sustain a low impact fx are also more likely to sustain another fx (Goulding, et al. J Peds 2005)  Fx rate in non-ambulatory children with CP = 4%/year; increases to 7%/yr if already had 1 fx (Stevenson, et al. Pediatr Rehabil. 2006) Alternate Sites: Lateral Distal Femur (LDF)

17. Alternate Sites: Lateral Distal Femur Align femur with table axis Foam blocks support leg not being scanned Sandbags help with stabilization From Zemel, et al. J Clin Densitom 2009 Comfortable side-lying position Less prone to movement artifacts Obtainable on most patients Quick <2 min scan time Can be acquired without sedation

18. The LDF scan is analyzed for 3 regions of interest: Region 1: Anterior distal metaphysis: essentially trabecular bone Region 2: Metadiaphysis: both trabecular & cortical bone Region 3: Diaphysis: primarily cortical bone Alternate Sites: Lateral Distal Femur (LDF)

19.  In children with physical disabilities, significant relationship between LDF bone density, fracture history, and ambulatory status (Harcke, et al. J Clin Neuromusc Dis 2006; Haas, et al, Dev Med Child Neurol 2012; Henderson, et al, JBMR 2013)  www.lateraldistalfemur.org Drawbacks  Scan modality not resident on machines – scans acquired in forearm mode  Manual analysis using subregions  Requires training on acquisition and analysis  Normative values for Hologic machine only (ages 6 – 18 years) Alternate Sites: Lateral Distal Femur (LDF)

20.  Pediatric LDF analysis uses growth plate landmark for placement of ROIs  Adult analysis technique developed and published  No adult normative data available yet Alternate Sites: Lateral Distal Femur (LDF) J Clin Densitom 2014

21. Candidates for Alternative Site Testing Limiting circumstances affecting acquisition: Musculoskeletal issuesContractures Inability to lie flat Movement disorders Behavioral problemsCognitive deficits Discomfort positioningSpinal Compression Fx Severe Scoliosis Skeletal Malformations ObesityPain Limited ROMPresence of artifacts (tubes, metallic hardware)

22.  Sample Diagnoses Cerebral PalsyPelizaeus Merzbacher Disease Rett SyndromeSpina Bifida Muscular DystrophySkeletal Dysplasias Genetic SyndromesOsteogenesis Imperfecta Candidates for Alternative Site Testing

23. Kecskemethy, et al, J Ped Rehab Med 2014 Candidates for Alternative Site Testing

24. Case study  18 year old with Pelizaeus Merzbacher Disease –Leukodystrophy, CNS involvement, delayed development through teens then deterioration, dysmyelination  Non-ambulatory/non-weight bearing  Scoliosis  Hx orthopedic surgery – left hip osteotomy with plate  Joint contractures  Baclofen pump (to decrease muscle tone)  No history of fractures  Eats by mouth; on Ca and Vit D supplements

25. Case Study

26. Z-scores -5.1 -6.3 -5.8 Z-scores -5.0 -6.2 -5.5 Summary DXA results LS (L1-L4)-5.3 RDF R1-5.0 RDF R2-6.2 RDF R3-5.5 LDF R1-5.1 LDF R2-6.3 LDF R3-5.8

27. Applying the use of DXA in non-standard ways  Alternative site testing used when standard sites are not available or more clinically relevant site desired  What if no sites available?  What if no norms available?  Do you still scan?

28.  Patients undergoing pharmacotherapy for low BMD and fracture  Each patient serves as their own control  Evaluate results for interval change over time  Examples: –Lateral spine BMD & BMC –BMD/BMC of site containing metal (as long as metal has not changed) –Subregion analysis Applying the use of DXA in non-standard ways

29.  Scan modality not available on all models of machines  No normative values  Each subject can serve as their own control to measure interval change over time  ROI placement can be challenging with small patients Applying the use of DXA in non-standard ways - Lateral Spine

30. Summary  Creative imaging is required for challenging patients and situations  Keeping reproducibility, precision and accuracy in mind is paramount  Understanding technical aspects of DXA is critical  Alternative site measures have value and should be considered if clinically justified  Obtaining appropriate training is important

31. Acknowledgements  H. Theodore Harcke, MD  Richard C. Henderson, MD, PhD  Steven J. Bachrach, MD  Nemours Departments of Medical Imaging and Biomedical Research  Families and Patients  ISCD Pediatric Bone Course Faculty  ISCD Meeting Planning Committee Questions?