Bone remodeling

Bone remodeling is the continuous lifelong coupled process of bone resorption and bone formation ^1-4. It is the prerequisite for repairing bony microdamage during daily physical activities, the adaption of bone architecture to meet different mechanical demands and the prevention of aging effects and accumulation of old bone ^2-4.

Terminology

Expansile remodeling is a radiological term that describes an adaptive bone remodeling process in response to the mechanical demand on the host bone in the presence of an adjacent bone tumor ^5-8.

Physiology

The remodeling process consists of various sequential phases and is controlled by several local and systemic factors. It involves several directly communicating cell types including osteocytes, bone-forming osteoblasts, bone-removing osteoclasts and their precursor cells that are organized and known as the basic multicellular unit (BMU) ^1-4.

Remodeling cycle

The remodeling cycle involves the following phases ^2-4:

• activation
  • detection of an initiating remodeling signal by different mechanisms such as
  • direct mechanical strain/damage to mineralized bone matrix leading (targeted remodeling)
  • hormone action on bone metabolism (non-targeted remodeling)
• resorption
  • recruitment of osteoclast precursors to the remodeling site
  • osteoclast differentiation and subsequent resorption activity
  • breakdown of mineralized bone matrix
• reversal
  • the transition from bone resorption to bone formation
  • disappearance of osteoclasts
  • removal of demineralized collagen and preparation of the bone surface by reversal cells
• formation and mineralization
  • replacement of osteoclastic cells with osteoblasts and new bone formation
  • creation of a collagen-rich osteoid matrix
  • deposition of hydroxyapatite crystals among the collagen fibrils
• termination and quiescence
  • cessation of the remodeling cycle after replacement of the resorbed bone matrix
  • differentiation of mature osteoblasts into bone lining cells, osteocytes or apoptosis

Regulation

Local/paracrine regulation

Local factors and signaling pathways that regulate the remodeling cycle include ^1-4:

• growth factors
• prostaglandins
• cytokines
• RANK/RANKL/osteoprotegerin
• Wnt

Systemic/endocrine regulation

The bone remodeling process is regulated by several systemic factors which include the following ^1-3:

• parathyroid hormone (PTH)
• vitamin D
• calcitonin
• thyroid hormone
• growth hormone
• glucocorticoids
• estrogen and androgens

History and etymology

The concept of the bone remodeling cycle has been substantially shaped by the work of American orthopedic surgeon Harold Frost (1921-2004) ^9,10.

Related pathology

Pathological conditions related to bone remodeling include the following ¹¹:

• primary and secondary osteoporosis
• renal osteodystrophy
• Paget disease of bone
• osteopetrosis
• rickets
• bone tumors