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Musculoskeletal Manifestations in the Setting of Chronic Renal Failure
Yatin Chadha
June 23, 2016
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Outline
Chronic Renal Failure
Renal Transplantation
Dialysis
- Renal osteodystrophy - Amyloidosis
- Spondyloarthropathy
- Osteonecrosis
- CIPS
- Gout
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Sorry eh!
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Normal Physiology
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Normal Physiology
PTH (Calcitonin)
P
Ca
Calcitriol PTH, P
-
P
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Normal Physiology
• Calcitriol
– Net effect : Ca & P
Absorption Turnover Ca & P
Absorption
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Normal Physiology
• PTH
– Net effect: Ca, P
Turnover Absorption Ca
Secretion P
Ca, P
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CRD - Pathophysiology
• Excretes excess P
P
PTH Ca Calcitriol
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Renal osteodystrophy/CKD-MBD
• Also referred to as chronic kidney disease – mineral bone disorder (CKD-MBD)
• Key player:
– 2° Hyperparathyroidism (HPT)
• Affects osteoblasts and osteoclasts
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Renal osteodystrophy/CKD-MBD
Bone loss
Bone formation Soft tissue Ca+
- Osteosclerosis - Periosteal neostosis
Focal resorption Generalized (osteomalacia, osteoporosis)
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Bone resorption in Renal Osteodystrophy
• Subperiosteal
• Cortical
• Endosteal
• Trabecular
• Subchondral
• Subphyseal
• Subligamentous & subtendinous
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Subperiosteal Resorption
Case courtesy Edward Smitaman
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Case courtesy Edward Smitaman
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Jalili P. Int Endodontic J. 2015
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Trabecular resorption
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Subchondral resorption
Case courtesy Edward Smitaman
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Subchondral resorption
Case courtesy Edward Smitaman Case courtesy Paul Fenton, Queen’s U.
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Subchondral and Subtendinous Resorption
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Subtendinous resorption
Murphey et al. Radiographics. 1993(2)
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Endosteal and Cortical Resorption
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Bone resorption – summary
• Earliest sign in 1° and 2° HPT • Subperiosteal resorption most common
(pathognomonic for HPT), responds to therapy • Sites:
– Subperiosteal: Radial aspects 2nd/3rd middle phalanges (pathognomonic), phalangeal tufts, femur, tibia, humerus, ribs, lamina dura
– Trabecular: skull (salt & pepper) – Subchondral: SI, AC, sternoclavicular, discovertebral, pubic
symphysis, patella – Subligamentous/tendinous: femoral trochanters, ischial
tuberosities, humeral tuberosities, conoid tubercle of clavicle, elbow, inferior calcaneus
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Brown Tumors (aka osteitis fibrosa cystica)
Osteoclasts Osteoblasts
Resorption/osteopenia Fibrovascular tissue ingrowth
Microfractures, hemorrhage, multinuclear macrophages
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Brown tumors - histopathology
• Fibrous stroma
• Multinucleated giant cells
• Hemorrhage/hemosiderin
Khalil et al. Eur J Med Res 2007
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Brown Tumors
• Occurs in 1° and 2° HPT, very uncommon
• Osseous resorption should co-exist
• Sites: Pelvic girdle, hands, extremities, ribs, clavicle, facial (can be multiple)
• Focal bone pain
• Imaging: – Well-defined, expansile
– MRI: low T2 signal, hemosiderin, enhancement
• Responds to therapy (sclerosis)
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Knowles et al. J Mag Res Imag. 2008 ;28 :759-761
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Generalized osteopenia
• Osteomalacia (reduced osteoid mineralization) – Imaging:
• Osteopenia • Poor trabecular/cortical distinction • Looser’s zones (femoral neck, pubic rami, ilium, ribs, scapulae,
acromion) • Rickets
• Osteoporosis
– Aluminum may also have a role – BMD screening not routinely recommended in 2°HPT – Fractures vertebrae, distal forearm, femur
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Osteomalacia
Lim CY. Clin Rad. 2013
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Increased bone density - osteosclerosis
• Axial skeleton > appendicular skeleton
– Spine (rugger jersey)
– Pelvis, calvarium, clavicles
– Metaphysis of long bones
• PTH action on osteoblasts
• Does not improve after dialysis
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Osteosclerosis
Case courtesy Edward Smitaman
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Esrd on dialysis 8 years
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Case courtesy Paul Fenton, Queen’s U.
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Bone formation – periosteal neostosis
• Late sign
• Mature periosteal bone formation with cleft
• Hand & feet, long bones, pelvis
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Soft tissue calcifications
• Periarticular
• Cartilaginous
• Arterial (pipestem, dorsalis pedis & radial)
• Visceral
• Ocular
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Periarticular calcifications
• Resemble tumoral calcinosis • Metabolic panel (GFR, Ca, P) • Often large joints (hip, shoulder, elbow, wrist
foot) • Often symmetric • Imaging:
– Cloud-like – May be cystic with Ca+ sedimentation (more active) – No bony erosion
• Can improve following dialysis
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Case courtesy Paul Fenton, Queen’s U
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Chondrocalcinosis
• Sites:
– Knee
– Wrist
– Hip
– Pubic symphysis
– Shoulder
• More common in 1° than 2° HPT
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Arthropathy of Hyperparathyroidism
• Mixed features:
– Erosions
– Relative preservation joint space
– Periosteal whiskering
– Subperiosteal resorption coexists
Resnick. Radiology. 1974;110: 263-269
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Resnick and Kransdorf, Bone and Joint Imaging 3rd edition. 2005
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Dialysis-related Bone Disease
Aluminum toxicity
Dialysis-related amyloidosis
Erosive arthropathy
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Aluminum toxicity
• Main source is aluminum salts (bind phosphate)
• Aluminum in dialysate is now less of an issue
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Aluminum toxicity
• Osseous
– Osteomalacia
– Fractures (ribs, vertebrae, pelvis, hips, sternum, clavicles)
– Possible role in spondyloarthropathy, osteonecrosis
• Encephalopathy
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Amyloidosis 2° hemodialysis
• B2-microglobulin (B2-M)
• Three main forms:
– Peripheral (arthopathy)
– Destructive spondyloarthropathy
– Carpal tunnel syndrome
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Case courtesy Edward Smitaman
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Case courtesy Edward Smitaman
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Case courtesy Brad Entwistle, UWO
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Case courtesy Brad Entwistle, UWO
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Case courtesy Brad Entwistle, UWO
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Case courtesy Brad Entwistle, UWO
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Case courtesy Brad Entwistle, UWO
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Case courtesy Brad Entwistle, UWO
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Amyloidosis – peripheral arthropathy
• Chronic hemodialysis (> 5 years)
• Sites: hip, wrist, shoulder (periarticular location)
• Osseous and soft tissue involvement (includes bursa)
• May result in pathologic fracture
• Imaging: – Joint space narrowing late feature
– May show low T2 signal
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Destructive spondyloarthropathy
• Chronic hemodialysis (> 4 years)
• B2-M deposition in disc and posterior elements
• Other predisposing factors? – Parathyroid mediated subchondral bone
resorption
– Aluminum
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Destructive spondyloarthropathy
• Key findings:
– Disc space narrowing
– End plate erosions
– Lack of osteophytes
– Low T2 signal
– No fluid collections
Case courtesy Eman Alqahtani, UCSD
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Destructive spondyloarthropathy
• Key findings:
– Disc space narrowing
– End plate erosions
– Lack of osteophytes
– Low T2 signal
– No fluid collections
Case courtesy Eman Alqahtani, UCSD
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Destructive spondyloarthropathy
• Key findings:
– Disc space narrowing
– End plate erosions
– Lack of osteophytes
– Low T2 signal
– No fluid collections
Case courtesy Eman Alqahtani, UCSD
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Destructive Spondyloarthropathy
• Key findings:
– Disc space narrowing
– End plate erosions
– Lack of osteophytes
– Low T2 signal
– No fluid collections
Theodorou et al. Seminars in Dialysis. 2002; 15(4)
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Destructive Spondyloarthropathy – summary
• Sites: lower C-spine, craniocervical
• May be multilevel
• Often shows low T2 signal
• Rapidly progressive (months)
• Ddx
– Early: ankylosing spondylitis
– Advanced: infection, crystal
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Amyloid – carpal tunnel
• > 50% of patients with 10+ years dialysis
• Most common surgical indication in chronic dialysis
• Median > ulnar nerve
• Imaging:
– Cysts (lunate, scaphoid), joint space preserved
– Volar involvement > dorsal
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Kiss et al. AJR. 2005;105:1460-67
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Dialysis-related Amyloidosis - Summary
• B2 microglobulin
• Three manifestations:
– Peripheral arthropathy
– Destructive spondyloarthropathy
– Carpal tunnel syndrome
• Chronic dialysis (5+ years)
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Erosive Arthropathy of Dialysis
• Avg 5 years of dialysis
• Probably multifactorial – HPT, amyloid, CPPD,
aluminum
• Hands/wrists
– Radiocarpal, MCPs, DIPs
• Erosions with narrowing of
joint space
Cotton et al. Skel Rad. 1997(26)
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Bone Disease Post Renal Transplantion
Osteonecrosis
CIPS (calcineurin-inhibitor induced pain syndrome)
Crystal disease (gout)
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Osteonecrosis following renal transplantation
• Frequency of ON following transplantation has dramatically decreased with cyclosporine and tacrolimus
• 2 studies:
– 232 patients 11 with ON (4.7%)
– 326 patients 15 with ON (4.6%)
Takao et al. Rhematol Int. 2011;31:165-170 Hedri et al. Transplant Proc. 2007 May; 39(4): 1036-8
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ON following renal transplantation
• Main risk factors
– Cumulative steroid dose
– Acute rejection
• Hip > knee
• Timing
– 6 months onward (avg 3.5 years post transplant)
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Osteonecrosis
• In patients treated with steroids, osteonecrosis more common when femoral neck and intertrochanteric region contain more fat
Van De Berg et al. Eur J Radiol. 2006;58
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Calcineurin-inhibitor induced pain syndrome (CIPS)
• Reversible symmetric lower extremity pain following transplantation
• 1989 cyclosporine
• 2001 tacrolimus
• Solid organ and bone marrow transplant
• Frequency: 1.5-14%
• Timing: several weeks to > 1 yr post transplant
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CIPS
• Mechanism(s):
– Altered vascular tone & permeability marrow congestion
– Altered bone metabolism elevated alkaline phosphatase (ALP)
Edler GJ. Nephrology. 2006;11:560-567
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CIPS
• Workup
– Calcineurin-inhibitor serum level
• Normal in first 3 months (5-15 ng/dL)
• Trough levels not always elevated
– Alkaline phosphatase (ALP)
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CIPS - Imaging
• Xrays: – May be normal
– Epiphyseal osteoporosis
– Metaphyseal periosteal reaction
– Effusions
– Findings may persist following resolution of symptoms
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CIPS - Imaging
• Scintigraphy: – Uptake in flow and
delayed phases
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CIPS - Imaging
• MRI
– Edema around knees, ankles, feet (dependent)
– Symmetric
– Associated fractures
– Findings may outlast symptoms
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CIPS – MR Imaging
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CIPS - Treatment
• Calcium channel blocker (amlodipine)
• Alteration in immunosuppressive regimen
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CIPS
• DDx
– Osteonecrosis
– Complex regional pain syndrome/RDS
– Transient osteoporosis
– Infection
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Gout Following Renal Transplantation
• 7.6% - frequency of newly diagnosed gout within 3 years of renal transplantation (United States Renal Data System)
• Risk Factors
– Males, age
– BMI
– Cyclosporine vs. tacrolimus
– GFR (<44)
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Gout - Physiology
Hyperuricemia
pH Temperature
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Hyperuricemia in Renal Transplantation
• Cyclosporine > tacrolimus
– Increased uric acid reabsorption
– Decreased uric acid
secretion
• Other factors
– Diuretics
– Poor graft function
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Gout - Distribution
• Classic sites:
– 1st MTP, TMT, CMC, popliteal groove
• Post renal tranplantation:
– May see more proximal distribution
– Increased burden of tophi
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Post Renal Tranplant Bone Disease - Summary
• Osteonecrosis – incidence has dramatically decreased (~5%)
• CIPS – symmetric dependent lower extremity pain, marrow edema on MRI +/- fractures
• Gout – calcineurin-inhibitors predispose to hyperuricemia and more proximal distribution may be seen
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Thank you!
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• Theodorou et al. Imaging in Dialysis Spondyloarthropathy. Seminars in Dialysis. August 2002; 15(4):290-296
• Cotton et al. Natural history of erosive arthropathy of the hands in patients undergoing hemodialysis. Skeletal Radiology. 1997(26):20-26
• Takao et al. Incidence and predictors of osteonecrosis among cyclosporin or tacrolimus-treated renal allograft recipients. Rhematol Int. 2011;31:165-170
• Hedri et al. Avascular necrosis after renal transplantation. Transplant Proc. 2007 May; 39(4): 1036-8
• Van De Berg et al. Correlation between baseline femoral neck marrow status and the development of femoral head osteonecrosis in corticosteroid treated patients: a longitudinal study by MR Imaging. European Journal of Radiology. 2006;58:444-449.
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• Knowles et al. MRI Diagnosis of Brown Tumor Based on Magnetic Susceptibility. Journal of Magnetic Resonance Imaging. 2008; 28:759-761
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• Olson Km and Chew FS. Tumoral Calcinosis: Pearls, Polemics, and Alternative Possibilities. Radiographics 2006; 26: 871-885
• Goffin et al. Epiphyseal impaction as a cause of severe osteoarticular pain of lower limbs after renal transplantation. Kidney International. 1993;44:98-106
• Edler GJ. From marrow edema to osteonecrosis: common pathways in the development of post-transplant bone pain. Nephrology. 2006; 11:560-567