4 Pathophysiology of Fractures

Michael R. McClung

Summary
• There are multiple determinants of fractures, many of which are related to each
other by virtue of their increased prevalence with aging.
• Osteoporosis (or low bone mass) is a major risk factor for fractures, but it is not
the only factor.
• Appropriate strategies for decreasing fracture frequency include both pharrna-
cologic and non-pharmacologic approaches, which address the wide variety of
risk factors for fracture with which our patients present.

Fractures are the complication of osteoporosis, much as strokes are the complication
and result of hypertension. It is only through fractures that osteoporosis manifests its
clinical effects or has clinical relevance. Fractures occur in patients with decreased
bone strength and who experience an injury. Thus, the pathophysiology of fractures
encompasses a multitude of factors that determine bone strength (bone mass, bone
quality, age, skeletal geometry) and the frequency, nature, and effects of injuries
(Figure 4.1).Each of these factors becomes more prevalent with advancing age, result-
ing in the exponential increase in the prevalence of fractures related to osteoporosis
in elderly individuals. Understanding the determinants of fracture risk provides the
basis of appropriate and effective interventions to reduce fracture frequency and the
complications of osteoporosis.

Peak Bone Mass

The level of bone mass in adults is determined by the level of peak bone mass
acquired during skeletal maturation and by the rate and duration of bone loss that
occurs thereafter. Peak bone mass is attained by age 20-25 years and is influenced by
both genetic and environmental factors. The role of heredity in determining peak
bone mass is dominant and accounts for 60-80% of the variance in peak bone mass.
The effect is related in part to body size and build but also to other factors. Peak bone
mass can be optimized by various environmental factors, including nutrition (espe-
cially calcium and caloric intake), physical activity, and sex steroid status. The com-
bined effects of heredity and these environmental factors can be modified by medical
problems such as anticonvulsant and glucocorticoid use, anorexia nervosa, intestinal
malabsorption, type I diabetes, and chronic inflammatory conditions.

21

P. Geusens et al., Osteoporosis in Clinical Practice

© Springer-Verlag London Limited 2004
22 Osteoporosis in Clinical Practice

Decreased bone
strength

Bone turnover rate

Effects offalls

Mechanics offalling

Frequency offalls

Figure 4.1 Determinants offracture risk. Both skeletal and non-skeletal factors areimportant predictors and
determinants offracture risk.

Increased calcium intake in children and adolescents results in a modest increase

in bone mass, but the extent to which this affects final peak bone mass is not yet clear.
Growing children and young adults who habitually are more physically active have
higher bone mass than their sedentary peers. Young adults of both genders who
experience a delay in puberty or transient intervals of sex steroid deficiency after
puberty seem to have lower peak bone mass.

Bone Loss
Following the acquisition of skeletal maturity, bone mass is relatively stable during
young adult years, although some longitudinal stud ies suggest a very slow rate of
bone loss beginning as early as 30 years of age in both men and women. The deter-
minants of bone loss in healthy premenopausal women and young men, if it occurs,
are not known . In women, a clear change in skeletal status occurs at menopause. As a
consequence of estrogen deficiency, the rate of bone turnover increases and the
imbalance between resorption and formation widens . As a result, bone loss acceler-
ates to about 2% per year (measured by absorptiometric techniques). Within about
fiveyears, the rate of bone loss slows gradually to less than 1% per year. Recent stud ies
demonstrate that the rate of bone loss accelerates again in advanced age, perhaps as
a result of acquired inefficiencies of calcium balance, including decreased intake of
calcium and vitamin D, decreased solar exposure, impaired renal activation of vita-
min D, and intestinal resistance to active vitamin D metabolites. Indeed , older indi-
viduals frequently have subclinical vitamin D deficiency and/or secondary
hyperparathyroidism, which may drive osteoclastic bone resorption and bone loss.
This may explain the observation that calcium and vitamin D administration seems