To maintain a structural integrity, the skeleton needs to constantly remodel and repair the microcracks that develop both in cancellous bone, the “spongy” bone present in the vertebrae, pelvis, and metaphyses of long bones, and in cortical bone, the “compact” bone present in the diaphysis of the long bones and surrounding the cancellous bone in the vertebrae and pelvis.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a subsequent increase in bone fragility and susceptibility to fractures [13
Skeletal fragility can result from
failure to produce a skeleton of optimal mass and strength during growth; excessive bone resorption resulting in decreased bone mass and microarchitectural deterioration of the skeleton; or inadequate response to increased resorption during bone remodeling [15
The process of bone remodeling occurs in basic multicellular units (BMUs) which include OCs, OBs, and osteocytes and begins with the activation of hematopoietic precursors to become OCs, which normally requires an interaction with cells of the OB lineage.
OCs are members of the monocyte-macrophage family and are derived from the fusion of marrow-derived mononuclear phagocyte, the OC precursors (OCPs), which circulate in peripheral blood (PB) [16
]. These cells differentiate under the influence of two cytokines, namely, macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor k-B ligand (RANKL). RANKL expressed on OBs and stromal cells as a membrane-bound protein and cleaved into a soluble molecule (sRANKL) by metalloproteinase [17
] promotes differentiation and fusion of OCPs and activates mature OCs to reabsorb bone by binding to its specific receptor RANK. Osteoprotegerin (OPG), a soluble decoy receptor secreted by OBs and bone marrow stromal cells, competes with RANK in binding to RANKL, preventing its osteoclastogenic effect [17
Mature multinucleated bone resorbing OCs are recognized by the expression of key OC markers including TRAP [18
], calcitonin receptors [19
], cathepsin K [20
], pp60c-src [21
], matrix metalloproteinase 9 (MMP9) [22
], and the alpha V beta 3 integrin chains [23
Because the resorption and reversal phases of bone remodeling are short and the period required for OB replacement of the bone is long, any increase in the rate of bone remodeling will result in a loss of bone mass [15
]. Moreover, the larger number of unfilled Howship's lacunae and Haversian canals will weaken the bone, and excessive resorption can also result in complete loss of trabecular structures, preventing bone formation.
Aside from postmenopausal osteoporosis which affects 30% of woman, there are many causes of secondary osteoporosis which occurs in almost 30–60% of men and more than 50% of premenopausal women [25
]. Osteoporosis in children may be primary due to an intrinsic bone abnormality (usually genetic in origin) or secondary due to an underlying medical condition and/or its treatment. The most common condition in the former category is osteogenesis imperfecta in which there is an underlying abnormality in bone matrix composition, usually due to defective synthesis of type I collagen.
Instead, osteoporosis circumscripta, characterized by focal osteolytic lesions [26
], is a peculiar condition of Paget's disease, a skeletal disorder which affects 1-2% of adults over 50 [27
The evaluation of subjects presenting with osteoporosis should include a detailed history, physical exam, and laboratory testing for secondary causes of osteoporosis, according to the guidelines of the American Association of Clinical Endocrinologists (AACE) [29