With extended life expectancy, aging population in different regions of the world is facing almost epidemic incidence of osteoporosis. Causes are numerous; along with increased longevity, certain medications such as corticosteroids may have direct impact on bone mass; the same can be said about frequent routine obstetric interventions aiming to induce iatrogenic (surgical) menopause and changes in the way of life.
Estimated probability for future fractures in individuals over 50 is about 40% for female and 13% in male population. The biggest socio-epidemiological problem is hip fracture, taking in consideration high mortality rate, frequent sequels, and impaired quality of life; in addition, this type of fracture burdens society with high expenses of medical treatment (20-23). Osteoporosis, clinically well defined by low bone density (low BMD) and disrupted bone microarchitecture, (established by DXA measurements, with T- score below -2,5), leads to enhanced bone fragility, and consequent suspectibility for fractures (28). Fractures most often arise in locations characterized by previous quantitative and qualitative deterioration of trabecular bone.
Technological developments in bone mineral density (BMD) measurements have led to diagnostic criteria that are widely applied. The World Health Organization diagnostic criteria for osteoporosis includes a BMD that lies 2.5 standard deviations or more below the average value for young healthy women (a T-score of <-2.5 SD) [4, 5, 15, 16].
Markers of bone turnover are biochemical products released during bone formation or reabsorption. Commonly used bone resorption markers are degradation products of type I collagen 1 (5,6), but non-collagenous proteins such as osteoclast-derived enzyme tartrate-resistant acid phosphatase 5b (TRACP) have also been investigated as resorption markers.
These compounds may be easily determined (usually in blood or urine). They reflect bone metabolic activity although they themselves have no function whatsoever in regulation of skeletal metabolism. Markers of bone formation are direct or indirect products of the osteoblasts’ activity expressed during various phases of their maturation and function. Type I collagen is an important component of bone matrix, and osteoblasts secrete its precursor - procollagen during the bone formation. The terminal peptides at each end of the procollagen molecule, procollagen type 1 pro-peptide (P1NP) and procollagen type I C pro-peptide (PICP), are cleaved by enzymes during bone matrix formation and released into the circulation (9-11).
Osteocalcin is another very sensitive and specific bone formation marker, also produced by osteoblasts. It is main non-collagen product of bone matrix. Osteocalcin demonstrates high calcium binding properties and serve as a messenger for calcitriol and leukocyte esterase inhibitor. It is excreted by the kidneys and its fragments may also be measured in urine. Newly formed osteoid undergoes maturation followed by mineralization. During this phase osteoblasts secrete alkaline phosphatase (ALP) into the extracellular fluid that may be detected in serum. In healthy adults, however, about half of the measured ALP is of hepatic origin, while the other half derived from the bone. Bone-derived isoform (BALP) is now widely available. Bone-derived alkaline phosphatase is very specific and sensitive marker of enhanced bone metabolism and reliable index of effectiveness of the antiresorptive therapy (34).
The pyridinium cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), formed during the maturation of bone collagen, are present in significant amounts in bone and dentine. These compounds are released during bone resorption and excreted in urine in the free and peptide-bound forms without being metabolized. (36) The peptide-bound forms of PYD and DPD include the C-terminal and N-terminal cross-linking telopeptides (CTX, NTX) of the type I collagen. These molecules are also released into the circulation and subsequently excreted in urine (9). Estrogen deficiency, associated with menopause, results in age related increase in bone remodeling and imbalance between bone formation and resorption.