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Table 2 Skeletal characteristics and clinical course

From: Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series

Patient Treatment and clinical course Dual energy X-ray absorptiometry (DXA) T-scoresa Additional imaging Bone resorption and formation markers/biochemical indices Inflammatory markers Biopsy data
1 Intravenous zoledronic acid infusions
NED; progressive back pain requiring kyphoplasty
T-scores:
Lumbar spine, −2.1
Left femoral neck, − 1.2
Left total hip, −0.4
Right femoral neck, − 1.7
Right total hip, − 0.8
MRI: Multilevel compression fractures of T12-L5 vertebral bodies; bilateral posterolateral rib fractures; multiple nondisplaced pelvic fractures superimposed on underlying osteopenia. CTX: 1038 pg/mL (↑)
bsALP: 11.6 μg/L
Ca: 9.5 mg/dL
25OHD: 48 ng/mL
CRP: 1.0 mg/dL (↑)
ESR 12 mm/h
Transiliac bone biopsy:
Reduced cortical and trabecular thickness; no osteoblastic activity; increased eroded surface and osteoclastic resorptive activity.
2 Denosumab q6mo
Progressive metastatic disease requiring hospice care; now deceased
T-scores:
Left femoral neck, − 1.5
Left total hip, 0.1
VFA: Multiple wedge deformities 16.8% in T6, 13.6% in T7, 11.2% in T8, 18% in T9, 4.1% in T10, 6.9% in T12, 13.2% in L1.
CT chest 1/17: New compression deformity of the superior endplates of T2-T5 vertebral bodies
CTX: 537 pg/mL
bsALP: 13.1 μg/L
Ca: 8.9. mg/dL
25OHD: 37 ng/mL
N/A N/A
3 Conservative management with calcium and vitamin D optimization
NED, pain free
T-scores:
L-spine, − 0.9
Left femoral neck, − 1.8
Left total hip, − 1.2
CT scan: T12 compression fracture with evolving compression deformity at T11; biconcave deformities of lumbar vertebrae CTX: 335 pg/mL
bsALP: 8.7 μg/L
Ca: 9.4. mg/dL
25OHD: 18 ng/mL (↓)
N/A N/A
4 Systemic oral steroids
Adalimumab
NED; improved inflammatory arthritis but progressive left shoulder pain and lack of mobility; no additional resorptive lesions
T-scores:
L-spine, − 1.0
Left femoral neck, − 1.2
Left total hip, 0.2
1/3 radius, − 1.9
MRI shoulder: Severe erosive changes of the glenohumeral articulation CTX: 589 pg/mL (↑)
bsALP: 18 μg/L (↑)
Ca: 9.4. mg/dL
25OHD: 52 ng/mL
CRP: 2.7 mg/dL (↑)
ESR: 69 mm/h (↑)
No evidence of melanoma (S100, HMB-45 and melan-A stains negative). Trabecular bone with bone marrow fibrosis and a scattered, mixed inflammatory cell infiltration.
5 Systemic oral steroids
Progressive, metastatic disease; limited response to steroids, currently in hospice
N/A Hand X-ray: Loss of ossific densities related to the capitate and also hamate, loss of cortical outline of the capitate and hamate CTX: 877 pg/mL (↑)
bsALP: 24 μg/L (↑)
Ca: 8.8 mg/dL
25OHD: 51.8
CRP: 13.5 mg/L (↑)
ESR: 31 mm/h (↑)
N/A
6 NSAIDs, Intraarticular corticosteroids
Progressive, metastatic disease; good rheumatologic response to steroids, currently on carboplatin pemetrexed and bevacizumab
T-scores:
L- spine, 0.8
Left femoral neck, 0. 0
Left total hip, 0.8
MRI clavicle: Acromioclavicular joint arthrosis with disproportionate bone marrow edema affecting the distal, no visible fracture CTX: 681 pg/mL (↑)
bsALP: 17 μg/L (↑)
Ca: 8.8 mg/dL
25OHD: 22 ng/mL (↓)
CRP: 2.0 mg/dL (↑)
ESR: 32 mm/h (↑)
N/A
  1. aT-score criteria by DXA: > − 1, normal bone density; − 1 to − 2.4, osteopenia; < − 2.5, osteoporosis
  2. (L-spine) Lumbar spine, (N/A) Not applicable, (NED) No evidence of disease, (CT) computed tomography, (MRI) magnetic resonance imaging, (VFA) Vertebral Fracture Assessment
  3. Biochemical parameters, normative levels: C-telopeptides (CTX) < 10–584 pg/mL; bone-specific alkaline phosphatase (bsALP) 7.6–14.9 μg/L; calcium (Ca) 8.4–10.5 mg/dL; 25-hydroxy vitamin D (25OHD); C reactive protein (CRP) < 0.5 mg/dL; erythrocyte sedimentation rate (ESR) 1–20 mm/h