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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


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


Intravenous zoledronic acid infusions

NED; progressive back pain requiring kyphoplasty


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.


Denosumab q6mo

Progressive metastatic disease requiring hospice care; now deceased


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




Conservative management with calcium and vitamin D optimization

NED, pain free


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 (↓)




Systemic oral steroids


NED; improved inflammatory arthritis but progressive left shoulder pain and lack of mobility; no additional resorptive lesions


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.


Systemic oral steroids

Progressive, metastatic disease; limited response to steroids, currently in hospice


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 (↑)



NSAIDs, Intraarticular corticosteroids

Progressive, metastatic disease; good rheumatologic response to steroids, currently on carboplatin pemetrexed and bevacizumab


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 (↑)


  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