The human skeleton is comprised of a mixture of collagen (type 1), non-collageneous matrix proteins and minerals; mainly calcium and phosphate, but also magnesium. Bone structurally needs to be stiff in order to allow for mechanical loading, but also flexible enough to absorb energy during impact loading and muscle contraction. When the balance between bone stiffness and flexibility is exceeded, fracture results.

Normal bone comprises an external outer periosteal layer and internal endosteal bone. The endosteal bone contains a mixture of cortical and trabecular (cancellous) bone, of varying amounts depending on the bone site. For instance the vertebral bodies predominantly contain trabecular bone, the radius predominantly contains cortical bone, while the hip comprises a mixture of both.

Bone is an active organ. There is a constant interplay between bone modelling (formation) and remodelling (breakdown). Within bone there are BMU (bone modelling units or basic multicellular units), which contain osteoblast cells, responsible for bone formation and osteoclasts, responsible for bone breakdown. Throughout life the process of bone formation and breakdown is constantly occurring which leads ultimately to alterations in the size, shape, architecture, mass and strength of bone.

Periosteal bone formation results in thickening of the periosteum and consequently increases in cortical bone thickness which increases the cross sectional area of bone.³

Within the endocortical bone surface, formation and resorption determine the proximity of endocortical and periosteal surfaces, with formation leading to increased cortical thickness and resorption leading to cortical thinning. This cortical thinning is partially compensated for by new periosteal bone formation.³ The trabecular bone being the more porous bone contains trabecular struts. Bone formation increases the thickness of the struts and resorption leads to thinning of the struts and even perforation of the struts.³

During the process of growth in childhood and adolescence, bone increases in size, with there being a small but proportional increase in bone density.³ Appendicular (limbs) growth dominates childhood growth and tends to precede axial growth (vertebral column) growth during puberty. It is during puberty that sex differences emerge in regards to skeletal development. As males have a later onset puberty than females (14 vs 12 years), there consequently is a persistence of appendicular growth in males for a longer period which results in males having longer limb bones than females without there being a great difference in truncal length between the two sexes.³ Males also have a greater cortical width than females primarily due to the fact that periosteal bone formation is greater in males than females. This is due to the fact that androgens, growth hormone and IGF-1 stimulate periosteal bone formation whereas oestrogen inhibits periosteal bone formation. However, this is partially offset in females by the fact that oestrogen stimulates endosteal bone formation. ⁴ It is also known that oestrogen is an important hormone in males for bone development.

Oestrogen plays a role in stimulating pubertal growth in females and males and epiphyseal closure at the completion of growth in both sexes. Oestrogen functions to increase bone mass in pubertal males, in addition to the effects of androgens.^{4, 5} Males who have a mutation of the oestrogen receptor, or inability to aromatise testosterone to oestrogen despite normal testosterone levels, not only have failure of epiphyseal closure, but also significantly low bone mineral density.^5-7 Hence oestrogen plays a role in skeletal development in both sexes.

As a consequence of sex differences within the skeleton, men have longer and wider bones, with only a slightly thicker cortex than females. In addition there are also structural differences within the long bones of males, which confer greater strength to male long bones in order to withstand the increased forces associated with muscle contraction.³

The skeleton undergoes defined changes as a result of normal ageing. Bone resorption occurs in both cortical and trabecular bone. Trabecular bone thins and may perforate and cortical bone also thins and may become porous. Periosteal bone formation partially offsets cortical bone thinning. As periosteal bone formation is greater in men, this ultimately results in men having less net bone loss than women.

All individuals undergo involutional (age-related) bone loss as part of normal ageing.

Women in particular undergo two phases of bone loss - an accelerated phase and a slow phase. The accelerated phase occurs at the time of menopause and is due to oestrogen deficiency.⁴ Although, this phase is recognised to occur at the time of menopause, it actually begins in the premenopausal years, as this is a time when oestrogen levels begin to fall.^8,9 This phase predominantly affects trabecular bone and results in approximately a 20 - 30% loss of trabecular bone mass. Cortical bone is also lost during this phase, but to a lesser degree, in the order of 5 - 10%. The accelerated phase lasts 4 - 8 years after the onset of menopause.⁴ In addition to oestrogen, androgens also play a vital role in the integrity of the female skeleton. Low androgen levels in the premenopausal years, have been found to also correlate with low bone density.¹⁰ In the peri- and postmenopausal years both low oestrogen and testosterone levels are associated with a reduced bone mass.¹⁰

The accelerated phase is followed by the slow phase and this phase is indefinite. It is characterised by reduced trabecular bone loss and either stable or increased cortical bone loss.⁴ This phase of bone loss is due to secondary hyperparathyroidism, which is a consequence of reduced calcium absorption from the gastrointestinal and renal systems. It results in compensatory increases in parathyroid hormone levels with the aim being to maintain serum calcium levels in the normal range.⁴ The bone loss in this phase is also contributed to by the effects of longstanding oestrogen deficiency and impaired osteoblast function, which is also due to the effects of oestrogen deficiency and ageing.⁴

In men involutional bone loss is predominantly due to the slow phase of bone loss except in the instance of castrated males, who will undergo an accelerated phase of bone loss similar to that of women. Males will lose approximately 20-25% of both cortical and trabecular bone mass during this phase. This is primarily due to the effects of secondary hyperparathyroidism.⁴ Due to the fact that males have greater periosteal bone formation, the amount of bone loss in males is less than in women.³

Overall, osteoporosis ultimately affects more women than men and this is primarily due to the sex differences between the male and female skeleton. As men have larger and longer bones and greater periosteal bone formation and are likely to have trabecular thinning rather than perforation of trabecular struts as in women, their bones are more resistant to the effects of involutional bone loss. Also as women undergo an accelerated phase of bone loss at the time of menopause this further reduces their bone mass and predisposes them to osteoporosis.

Content updated July 28, 2009