Bone Remodeling

The interplay between bone formation and resorption is a continuous lifelong process which favors bone formation in the early years of life, leading to a peak bone mass at approximately 20 to 30 years of age. From there on, the total bone mass gradually declines in both men and women.

Some women experience an increased rate of bone loss in the early post-menopausal years. The cycle of bone remodeling starts with osteoclasts (resorption cells) eroding bone surfaces, thereby forming cavities. This results in the release of collagen degradation by-products into the circulation system, such as pyridinoline and deoxypyridinoline cross-links, hydroxyproline and N- and C-collogen telopeptides.

At the same time, osteoblasts (bone-forming cells) secrete bone matrix proteins, 90% of which are collagen type I with other minor proteins, as well as the hormone osteocalcin and the bone-specific isoenzyme of alkaline phosphatase and procollagen I extension peptides, which are secreted into general circulation. The final step in the cycle is the mineralization of the matrix protein by calcium salts.

Additional mechanical bone tensile strength is attained by the formation of pyridinuum cross-links (pyridinoline [Pyd] and deoxypyridinoline [DPD]) between the neighboring mature collagen fibrils.

Osteoporosis

Osteoporosis is a relatively irreversible disease with complications that can be detrimental. Its pathogenesis is the result of a dynamic chronic imbalance among a variety of factors.

Hormones Tested

Estrogen

• Limit bone elongation in adolescents and prevent bone loss in adults.
• After menopause very small amounts of estrogens, if any, are secreted by the ovaries.
• Low estrogen levels cause diminished bone deposition.
• Low estrogen levels increase the number and activity of osteoclasts.

Progesterone

• Promotes new bone formation and deposition.

Testosterone

• Helps reduce bone loss, and has a role in bone formation.

Cortisol

• Glucocorticoids directly inhibit bone formation by decreasing cell proliferation and the synthesis of DNA, protein and collagen.
• Glucocorticoid-induced bone loss results from lower activity and higher death rate of osteoblasts on the one hand, and from increased bone resorption due to prolonged life span of osteoclasts on the other.
• Glucocorticoids may potentiate the proresorptive actions of parathyroid hormone and Vitamin D on bone, which contribute to net bone resorption.

FSH

• Bone loss during or after menopause has been attributed to a drop in estrogen levels. Recent studies show that high FSH is required for hypogonadal bone loss.
• In early menopause, FSH levels show a sevenfold increase over values found in young menstruating women.
• In perimenopause and postmenopause, FSH is correlated with:
  • Bone loss and osteoporosis.
  • Sleep disturbances.
  • Hot flashes and night sweats.

DHEA/DHEA-S

• Enhances bone deposition and remodeling.
• Decreases bone resorption and increases bone formation.

DPD

• Type I collagen degradation by-product— a marker for bone resorption.

Diagnosis of Osteoporosis

The best approach to osteoporosis is prevention, especially in patients who are high risk. The diagnosis of osteoporosis relies heavily on bone densitometry (mineralized bone mass) using radioactive or x-ray techniques. However, the diagnostic modalities in use today have limitations in reliability and reproducibility, specifically in fracture prediction capability.
Recent technology has allowed the development of urinary assays for bone resorption markers as a complementary method to bone mineral density in the diagnosis and follow-up of osteoporotic patients.

Indications

• Preliminary screening in patients with high risk for osteoporosis.
• Therapeutic monitoring during and after trea™ent for osteoporosis.
• As an adjunct tracking tool in bone and mineralization assessment after initial densitometry is performed.
• Follow-up for monitoring efficacy of hormone replacement therapy in the prevention of osteoporosis in both sexes.
• Hip-fracture risk prediction in the elderly.
• Preliminary screening for estrogen-deficient women at clinical risk for osteoporosis.
• Preliminary screening for individuals receiving or planning to receive long-term glucocorticoid therapy.
• Preliminary screening for metabolic bone diseases.
• Preliminary screening for rheumatoid arthritis and other connective tissue disease.
• Preliminary screening for Paget’s disease.
• Preliminary screening for bone malignancies.