by Dr. Elza Coetzee
PATHCHAT Edition No. 1
Please contact your local Ampath pathologist for more information.
Definition of Osteoporosis
The World Health Organisation (WHO) defines osteoporosis (OP) as:
"A systemic skeletal disease characterised by reduced bone mass and micro-architectural deterioration of bone tissue that results in decreased bone strength and increased risk of fractures, which usually involves the wrist, hip, vertebrae, pelvis, ribs, or humerus."
Why is Osteoporosis Important?
- 9 million fractures occur worldwide annually due to osteoporosis.
- Lifetime risk of an osteoporotic fracture after age 50:
- 40% in women
- 20% in men
- 50% of patients with fractures never regain full functionality.
- 20% of patients die within one year of an osteoporotic fracture.
The WHO predicts a threefold rise in osteoporosis cases over the next 50 years due to aging populations.
Overview of Osteoporosis
Osteoporosis is a bone disease characterized by increased bone turnover and reduced bone density.
Normal vs. Osteoporotic Bone
In Healthy Bone:
- Osteoclasts resorb bone (process takes 2 weeks).
- Osteoblasts deposit new bone (takes 6 months).
- Mineralization follows to strengthen the bone.
In Osteoporosis:
- Bone remodeling cycles occur faster, leading to an imbalance.
- Resorption exceeds formation, making bones weak and fragile.
- This results in soft bones prone to fractures.
Primary vs. Secondary Osteoporosis
Osteoporosis can be primary (due to aging or menopause) or secondary (caused by another condition or medication).
Common Causes of Secondary Osteoporosis:
Endocrine Causes
- Hypogonadism
- Hyperthyroidism
- Cushing’s Syndrome
Gastrointestinal Causes
- Partial gastrectomy
- Malabsorption
- Chronic liver diseases
Drug-Induced Osteoporosis
- Glucocorticoids
- Anticonvulsants
- Heparin
- Methotrexate and other chemotherapies
- Alcohol & tobacco
Autoimmune Diseases
- Rheumatoid arthritis
- Systemic lupus erythematosus
Hematological Causes
- Multiple myeloma
- Monocytic leukemia
Diagnosis of Osteoporosis
The gold standard for diagnosing osteoporosis is Bone Mineral Densitometry (BMD) using Dual-Energy X-ray Absorptiometry (DEXA).
WHO Classification of Osteoporosis (Based on BMD T-Scores)
- Normal: T-Score above -1
- Osteopenia: T-Score between -1 and -2.5
- Osteoporosis: T-Score below -2.5
- Severe Osteoporosis: T-Score below -2.5 + one or more fragility fractures
Did you know? Many patients with osteoporotic fractures do not have a T-score below -2.5, meaning they may not receive treatment under traditional guidelines.
Additional Risk Factors for Osteoporosis
- Age
- Gender
- Race
- BMI (Low Body Mass Index)
- Physical inactivity
- Family history of fragility fractures
- Poor nutrition
A more accurate risk assessment can be achieved using FRAX® (Fracture Risk Assessment Tool).
Biochemical Markers in Osteoporosis
Biochemical markers are useful for assessing fracture risk and monitoring treatment progress.
Key Bone Turnover Markers:
Bone Formation Markers
- Bone-specific ALP (B-ALP)
- Osteocalcin
Bone Resorption Markers
- Beta-crosslaps (CTX)
Why Are Bone Turnover Markers Important?
- Provide early detection of high-risk patients.
- Help monitor treatment adherence and assess therapy effectiveness.
- Show treatment response much sooner than DEXA scans.
Treatment Success Indicators:
- 50% decrease in bone resorption markers (CTX) within 3-6 months → Indicates effective therapy.
- 50% decrease in bone formation markers (B-ALP, Osteocalcin) within 6-12 months → Confirms effective therapy.
DEXA scans take 2 years to show improvement, while biochemical markers can show results in just a few months!
Osteopenia vs. Osteoporosis
Osteopenia (low bone mass) is often due to Vitamin D deficiency (osteomalacia) or Primary hyperparathyroidism.
Comparison: Osteopenia vs. Osteoporosis
Osteopenia:
- T-Score: -1.0 to -2.5
- Common Causes: Vitamin D deficiency, Hyperparathyroidism
Osteoporosis:
- T-Score: Below -2.5
- Common Causes: Increased bone turnover, Aging
Up to 20% of patients with osteoporotic hip fractures have underlying osteomalacia!
Laboratory Tests for Osteoporosis Screening
Bone Turnover Markers
- B-ALP, Osteocalcin, Beta-crosslaps (CTX)
Calcium & Phosphate Metabolism
- Calcium, Phosphate, Albumin, PTH, Vitamin D (25OHD)
Endocrine Function Tests
- TSH, Estradiol, FSH, LH (women), Testosterone (men)
Hematological Markers
- Full Blood Count (FBC), ESR, Serum Protein Electrophoresis
Liver & Kidney Function
- AST, ALT, Creatinine
Conclusion: A Practical Approach to Biochemical Assessment of Osteoporosis
Routine Screening Includes:
- DEXA Scan + Clinical Risk Factors
- Bone Turnover Markers:
- B-ALP or Osteocalcin
- Beta-crosslaps (CTX)
- Tests for Bone Mineralization Defects:
- Vitamin D (25OHD), PTH, Calcium, Phosphate, Albumin
- Tests for Secondary Causes of Osteoporosis:
- Full blood count, ESR, Creatinine, ALP, AST/ALT, Serum Protein Electrophoresis, TSH, Estradiol/FSH/LH (females), Testosterone (males)
Monitoring Treatment Response:
- Beta-crosslaps (CTX) decrease by 50% in 3-6 months → Effective therapy.
- Bone ALP/Osteocalcin decrease by 50% in 6-12 months → Effective therapy.
References
- Hough S, Ascott-Evans B, et al. "NOFSA Guideline for the Diagnosis and Management of Osteoporosis." Journal of Endocrinology, Metabolism and Diabetes of South Africa, 2010.
- World Health Organisation. "Assessment of Osteoporosis at Primary Healthcare Level." WHO Study Group, 2004.
- Cundy T, Reid I. "Metabolic Bone Disease." Clinical Biochemistry: Metabolic and Clinical Aspects, Churchill Livingstone, 1995.