Bone thinning disorders
Osteoporosis
Description
Causes
- Most common cause
- ↑ Bone resorption (↑ osteoclast number and activity) due to factors like low estrogen levels, old age, cigarette smoking.
- Secondary causes
- Drugs (e.g., steroids, alcohol, anticonvulsants, anticoagulants, thyroid replacement therapy, PPI)
- Conditions (e.g., hyperparathyroidism, hyperthyroidism, multiple myeloma, malabsorption syndromes, anorexia).
- Low BMI (or weight)
- Prolonged microgravity exposure (eg, space travel)
- UWT of medications associated with osteoporotic fractures
<aside>
🧩
Perimenopausal woman with fragility fracture→ Check drug history.
</aside>
<aside>
🧠
PPI (omeprazole) decreases Ca absorption which leads to osteoporosis.
</aside>
Diagnosis
- Fragility fracture (e.g., fall from standing height, minimal trauma).
- Radiology
- Bone mineral density measurement by DEXA (dual-energy x-ray absorptiometry).
- Sites of measurement→ lumbar spine, total hip, and femoral neck.
- Diagnostic score→ T-score of ≤ −2.5
- Lab values
- Normal serum Ca²⁺ and PO₄³⁻
<aside>
💡
One-time screening recommended for females ≥ 65 years old.
</aside>
Complications

Treatment
- Bisphosphonates
- Teriparatide
- SERMs (selective estrogen receptor modulators)
- Denosumab (monoclonal antibody against RANKL)
- Romosozumab (sclerostin inhibitor)
Prophylaxis
- Regular weight-bearing exercise
- Adequate Ca²⁺ and vitamin D intake throughout adulthood.



Osteomalacia/Rickets

Pathogenesis
- Vitamin D deficiency leads to ****defective mineralization of
- Osteoid in adults→ osteomalacia
- Cartilaginous growth plates in children→ rickets
Presentation in children with rickets
- Pathologic bow legs (genu varum)
- Beadlike costochondral junctions (rachitic rosary)
- Craniotabes (soft skull)
Diagnosis
- X-ray Findings
- Osteomalacia
- Osteopenia
- Pseudofractures.
- Rickets
- Epiphyseal widening
- Metaphyseal cupping/fraying.
- Laboratory Findings
- ↓ Vitamin D → ↓ serum Ca²⁺ → ↑ PTH secretion → ↓ serum PO₄³⁻
- Hyperactivity of osteoblasts→ ↑ serum ALP.
Types of rickets
- Rickets can be categorized as calcipenic (low calcium) or Phosphopenic (low phosphorus).
- Calcipenic rickets can be due to
- Low calcium intake
- Deficiency or metabolic disorders (eg, receptor defects) of vitamin D.
- Phosphopenic rickets mostly due to
- Primary defect in renal phosphate reabsorption (eg, hereditary hypophosphatemic rickets)



Bone thickening disorders
Osteopetrosis
Description
- Inherited defect of bone resorption resulting in abnormally thick, heavy bone that fractures easily.
Pathophysiology
- Mutations (e.g., carbonic anhydrase II) impair osteoclast ability to generate acidic environment for bone resorption→ thickened, dense bones prone to fracture.
Presentation
- Bone fractures
- Overgrowth of cortical bone fills marrow space→ pancytopenia and extramedullary hematopoiesis.
- Cranial nerve impingement due to narrowed foramina→ Vision and hearing impairment.
Diagnosis
- X-ray
- Diffuse symmetric sclerosis (bone-in-bone, "stone bone").
- Histology
Treatment
- Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes.
Osteitis Deformans (Paget Disease of Bone)

Description
Lab Values in Bone Disorders (Top HY)