Bone diseases
Osteonecrosis
ON refers to death of the cellular component of bone (osteocytes) and the bone marrow
resulting from ischemia. 2-5%, mostly in men around 50s. Can happen in the medullary or
trabecular bone. 5-10% of total hip replacements are due to AVN.
Causes:
Drugs: GCs,
Alcohol
SLE: because of GC use and concomitant aPS
JIA
aPS
Coagulopathies: thrombophilia, thrombotic syndromes
Hemoglobinopathies: sickle cell vasoocclusion
Infiltrative diseases: Gaucher, amyloidosis, histiocytosis
Pregnancy
Renal disease: amyloidosis, uremic coagulopathy
Infections
Protease inhibitors (HIV)
*anti-osteoporotic drugs: zoledronic IV, DEN → osteonecrosis of the jaw
Pathophysiology: necrosis of all cellular components of bone, both in hematopoietic fat
marrow and mineralized tissue. Focal bone death results from a impaired arterial blood supply.
•Altered fat metabolism (GC, alcohol, renal disease): promote differentiation of
mesenchymal stem cells to adipocytes, so the amount of fat within the femoral head increases
and elevates intracortical pressure and leads to venous sinusoids compression, intravascular
coagulation, arterial blood flow blockage and ischemia. Both have adverse influences on bone
cell lineage by enhancing adipogenesis and inhibiting osteoblastogenesis by marrow stem cells.
They also induce hypertrophy of the adipocyte through increasing intracellular lipid synthesis.
GCs upregulate PPAR-γ2 which pushes mesenchymal cells to
differentiate to adipocytes, therefore contributing to GIOP (thiazolidinediones also do this).
•Direct cell death: GCs, alcohol.
•Vessel occlusion: thrombi, fat emboli or abnormally shaped RBCs (sickle cells).
•Infiltrative mechanisms: amyloidosis, histiocytosis, Gaucher, lymphomas.
•Defective reparative and revascularization mechanisms.
•Trauma / fracture
Imaging: regional and highly circumscribed. It can be confined to a medullary section of
bone or involve a periarticular segment such as the subcortical femoral head. Subchondral
fracture, when present, is usually located in the dead bone, typically somewhat parallel to the
edges of the articular surface, which results in the characteristic radiologic “crescent sign”.
MRI: a typical area of normal marrow signal on T1/T2 is bordered by a dark
line/rim. Over time, T2-bright signal parallels the inside margin of the lesion, a sign often
referred to as the characteristic “double-line” sign (75%). The subchondral fracture line may
appear bright on T2 and dark on T1. Over time, the lesion, if not revascularized, will appear dark
on both T1 and T2 images. Additionally, effusion is seen in ~60%.
Classification: Ficat and Arlet classification
Stage I - Rx: normal or minor osteopenia, MRI: BME
Stage II - Rx: sclerosis ± subchondral cysts
, Stage III - crescent sign, cortical collapse
Stage IV- OA
Scintigraphy: subchondral “cold spot” (avascular necrosis) surrounded by a
“hot” area (donut sign) where there is increased osteoblastic activity at the interface with the
necrotic bone. Note that be can be negative in 25-45%!
Clinical: typical sites: femoral head (the most common), femoral condyles (knee), the
proximal tibia, the humeral head, the small bones of the foot and ankle, the wrist (lunate
necrosis =‘Kienbock’s disease’, scaphoid necrosis = ‘Preiser's disease’), the vertebrae, the jaw.
When confined to medullary bone may be asymptomatic! In childhood: Legg-Calve-Perthes:
ANV of the epiphysis of the femoral head, more common in boys (5:1), 4-10yrs.
Red flags (when to think of AVN): it is differentiated from ordinary joint pain by its
severity, presence at rest, pain at night, lack of relationship to weight bearing and (in early
stages) preservation of joint RoM.
Complications: collapse of the joint surface and secondary OA.
Dx
Bone infarct: an osteonecrosis occurring in the diaphysis or metadiaphysis of the bone. The
characteristics differ from typical epiphyseal osteonecrosis but share many predisposing factors.
Subchondral insufficiency fracture: typically, these are located in the medial or lateral femoral
condyle or tibial plateau and may be associated with knee pain that differs in character from
that of OA pain in its intensity and presence also during non weight-bearing activities.
MRI, there is typically BME in the region of the fracture and often meniscal damage. A
low signal intensity area is seen on T1, with corresponding to high signal intensity on fluid-
sensitive sequences, reflecting a fracture line. It may evolve into secondary osteonecrosis.
Osteonecrosis during pregnancy: can be confused with transient osteoporosis of the hip
during pregnancy.
Transient osteoporosis of the hip: it also has Rx demineralization, no fracture line, no necrosis
Infectious
Malignancy (metastases also)
Treatment: avoid weight-bearing, analgesics, Salospir, bisphosphonates, hyperbaric O2,
core decompression. Teriparatide can be an option for ONJ (but data come from studies of
dubious quality). Therapy with statins may inhibit GC-induced adipogenesis and osteonecrosis of
the femoral head, but data are not consistent, as some studies confirm it, while others don’t.
Also, extracorporeal shockwave therapy has varying levels of efficacy reported.
Bone marrow edema syndromes
Bone marrow edema (BME) syndromes are a group of entities characterized by BME on MRI.
Note that in reality it’s the subchondral bone that is affected and not the bone marrow. MRI is
positive 48h after pain onset! Bone scintigraphy is highly sensitive but not specific (in contrast
with scintigraphy in AVN that’s up to 50% negative).
Transient osteoporosis of the Hip (TOH)
most commonly affects middle-aged men with a male to female ratio of 3:1 and is primarily
characterized by BME and acute-onset pain. The hallmark that separates transient osteoporosis
from other conditions presenting with BME lies in the self-limited nature of TOH and the
regional osseous demineralization detected on plain radiographs (osteoporosis). Good prognosis
with complete restoration of bone density. Recurrence possible, follow up for 2 years.
Osteonecrosis
ON refers to death of the cellular component of bone (osteocytes) and the bone marrow
resulting from ischemia. 2-5%, mostly in men around 50s. Can happen in the medullary or
trabecular bone. 5-10% of total hip replacements are due to AVN.
Causes:
Drugs: GCs,
Alcohol
SLE: because of GC use and concomitant aPS
JIA
aPS
Coagulopathies: thrombophilia, thrombotic syndromes
Hemoglobinopathies: sickle cell vasoocclusion
Infiltrative diseases: Gaucher, amyloidosis, histiocytosis
Pregnancy
Renal disease: amyloidosis, uremic coagulopathy
Infections
Protease inhibitors (HIV)
*anti-osteoporotic drugs: zoledronic IV, DEN → osteonecrosis of the jaw
Pathophysiology: necrosis of all cellular components of bone, both in hematopoietic fat
marrow and mineralized tissue. Focal bone death results from a impaired arterial blood supply.
•Altered fat metabolism (GC, alcohol, renal disease): promote differentiation of
mesenchymal stem cells to adipocytes, so the amount of fat within the femoral head increases
and elevates intracortical pressure and leads to venous sinusoids compression, intravascular
coagulation, arterial blood flow blockage and ischemia. Both have adverse influences on bone
cell lineage by enhancing adipogenesis and inhibiting osteoblastogenesis by marrow stem cells.
They also induce hypertrophy of the adipocyte through increasing intracellular lipid synthesis.
GCs upregulate PPAR-γ2 which pushes mesenchymal cells to
differentiate to adipocytes, therefore contributing to GIOP (thiazolidinediones also do this).
•Direct cell death: GCs, alcohol.
•Vessel occlusion: thrombi, fat emboli or abnormally shaped RBCs (sickle cells).
•Infiltrative mechanisms: amyloidosis, histiocytosis, Gaucher, lymphomas.
•Defective reparative and revascularization mechanisms.
•Trauma / fracture
Imaging: regional and highly circumscribed. It can be confined to a medullary section of
bone or involve a periarticular segment such as the subcortical femoral head. Subchondral
fracture, when present, is usually located in the dead bone, typically somewhat parallel to the
edges of the articular surface, which results in the characteristic radiologic “crescent sign”.
MRI: a typical area of normal marrow signal on T1/T2 is bordered by a dark
line/rim. Over time, T2-bright signal parallels the inside margin of the lesion, a sign often
referred to as the characteristic “double-line” sign (75%). The subchondral fracture line may
appear bright on T2 and dark on T1. Over time, the lesion, if not revascularized, will appear dark
on both T1 and T2 images. Additionally, effusion is seen in ~60%.
Classification: Ficat and Arlet classification
Stage I - Rx: normal or minor osteopenia, MRI: BME
Stage II - Rx: sclerosis ± subchondral cysts
, Stage III - crescent sign, cortical collapse
Stage IV- OA
Scintigraphy: subchondral “cold spot” (avascular necrosis) surrounded by a
“hot” area (donut sign) where there is increased osteoblastic activity at the interface with the
necrotic bone. Note that be can be negative in 25-45%!
Clinical: typical sites: femoral head (the most common), femoral condyles (knee), the
proximal tibia, the humeral head, the small bones of the foot and ankle, the wrist (lunate
necrosis =‘Kienbock’s disease’, scaphoid necrosis = ‘Preiser's disease’), the vertebrae, the jaw.
When confined to medullary bone may be asymptomatic! In childhood: Legg-Calve-Perthes:
ANV of the epiphysis of the femoral head, more common in boys (5:1), 4-10yrs.
Red flags (when to think of AVN): it is differentiated from ordinary joint pain by its
severity, presence at rest, pain at night, lack of relationship to weight bearing and (in early
stages) preservation of joint RoM.
Complications: collapse of the joint surface and secondary OA.
Dx
Bone infarct: an osteonecrosis occurring in the diaphysis or metadiaphysis of the bone. The
characteristics differ from typical epiphyseal osteonecrosis but share many predisposing factors.
Subchondral insufficiency fracture: typically, these are located in the medial or lateral femoral
condyle or tibial plateau and may be associated with knee pain that differs in character from
that of OA pain in its intensity and presence also during non weight-bearing activities.
MRI, there is typically BME in the region of the fracture and often meniscal damage. A
low signal intensity area is seen on T1, with corresponding to high signal intensity on fluid-
sensitive sequences, reflecting a fracture line. It may evolve into secondary osteonecrosis.
Osteonecrosis during pregnancy: can be confused with transient osteoporosis of the hip
during pregnancy.
Transient osteoporosis of the hip: it also has Rx demineralization, no fracture line, no necrosis
Infectious
Malignancy (metastases also)
Treatment: avoid weight-bearing, analgesics, Salospir, bisphosphonates, hyperbaric O2,
core decompression. Teriparatide can be an option for ONJ (but data come from studies of
dubious quality). Therapy with statins may inhibit GC-induced adipogenesis and osteonecrosis of
the femoral head, but data are not consistent, as some studies confirm it, while others don’t.
Also, extracorporeal shockwave therapy has varying levels of efficacy reported.
Bone marrow edema syndromes
Bone marrow edema (BME) syndromes are a group of entities characterized by BME on MRI.
Note that in reality it’s the subchondral bone that is affected and not the bone marrow. MRI is
positive 48h after pain onset! Bone scintigraphy is highly sensitive but not specific (in contrast
with scintigraphy in AVN that’s up to 50% negative).
Transient osteoporosis of the Hip (TOH)
most commonly affects middle-aged men with a male to female ratio of 3:1 and is primarily
characterized by BME and acute-onset pain. The hallmark that separates transient osteoporosis
from other conditions presenting with BME lies in the self-limited nature of TOH and the
regional osseous demineralization detected on plain radiographs (osteoporosis). Good prognosis
with complete restoration of bone density. Recurrence possible, follow up for 2 years.
