Pathophysiology and Clinical Presentation- Correct Diagnosis

• Osteoporosis= Osteo (bone) + porosis (porous); a multifactorial disease resulting in decreased bone density, rendering it weaker and more prone to fracture
  • Primary (idiopathic)
  • Secondary (endocrine diseases, medications, tobacco/ethanol)
• Results from an imbalance in bone remodeling (McCance & Huether, 2019)

Bone Remodeling (Physiologic)

Remodeling or rebuilding occurs normally in the body to maintain bone homeostasis. Spongy bone, for example, is replaced every 3-4 years, and compact bone is replaced every 10 years. It can also occur after fracture or in an attempt to repair small cracks that occur to bones under stress, like after lifting heavy weights (McCance & Huether, 2019). The remodeling process relies on the delicate balance of two elements, resorption and formation. Two bone cells are instrumental in these steps, osteoclasts and osteoblasts (McCance & Huether, 2019). Resorption is the mechanism where osteoclasts break down bone tissue and release its minerals like calcium to the blood. Formation, on the other hand, is the creation of new bone by osteoblasts. Osteoblasts are also responsible for keeping osteoclasts in check (McCance & Huether, 2019).

RANKL/RANK/OPG Pathway

Remodeling relies on the balance of this system (McCance & Huether, 2019).

• RANKL: Cytokine, stands for “Receptor Activator of Nuclear Factor kB Ligand”
• RANK: Receptor for RANKL
  • Is stimulated by RANKL release from osteoblasts and subsequent binding
  • This results in osteoclast differentiation
  • More osteoclasts mean greater resorption, bone loss
• OPG: Glycoprotein “decoy receptor,” stands for “Osteoprotegerin”
  • Secreted by osteoblasts
  • Blocks the binding of RANKL to RANK receptors, resulting in decreased bone resorption
• Osteoclast production and apoptosis also affected by:
  • Interleukins
  • TNF-a
  • TGF-b
  • Prostaglandin E2
  • Hormones
• When this system becomes dysfunctional, bone loss > bone growth!
  • Example: osteoporosis (McCance & Huether, 2019).

Osteoporosis (Pathologic)

1. Post-Menopausal Osteoporosis
   Estrogen: sex steroid hormone that normally downgrades RANKL, increases OPG production, and activates extra-cellular signal-regulated kinases (ERKS) which induce apoptosis in osteoclasts; estrogen is diminished post-menopause
   ↑ RANKL
   ↓ OPG
2. Glucocorticoid-Induced Osteoporosis
   ↑ RANKL
   ↓OPG
3. Age-Related Bone Loss
   ↓  GH and IGF levels
   ↓ OPG secretion
   ↑ in binding of RANKL to RANK receptors (McCance & Huether, 2019)

Clinical Manifestations

• Asymptomatic until fractures occur
• Fractures
• Pain
• Loss of function
• Bone deformities
• Decreased height
• “Kyphosis,” or hunchback appearance (McCance & Huether, 2019)