2.3. Etiopathology of hip fractures

2.3.1. Age

The incidence of the hip fracture is closely related to age and increases almost exponentially, so that about 90% of hip fractures occur after age 70 (Cummings et al. 1989, Melton, III 1996). The lifetime risk for a woman aged 50 years is 14–18%, compared with 3–6% for a man (Cooper 1998). It is estimated that 30% of older adults will have a hip fracture by age 90. Normal postural stability deteriorates during aging because of changes in vision, vestibular function and the musculoskeletal system, and this contributes to the risk of falls as well as the types of falls (Birge et al. 1994). Bone loss affecting bone strength usually increases by aging (Cummings et al. 1990). Loss of weight during aging affects the local shock absorbers, reducing especially muscles and increasing the risk of fracture after the fall (Cummings & Nevitt 1989).

2.3.2. Sex

White women have a twofold risk compared to white men, while black women and men are at similar risk (Farmer et al. 1984). The cross-sectional geometry of the lower limb bones including the femur may play an important role in the differences of the hip fracture risk between women and men. Men undergo greater subperiosteal expansion upon aging than women and the cortical area remains almost constant in men, but decreases in women. Thus, age-related changes in bone cross-sectional geometry appear to compensate for age-related reductions in bone strength in men but not in women (Mow & Hayes 1991). The absence of a distinct equivalent of menopause with associated acceleration of bone loss in men, their shorter life expectancy, and their reduced propensity to fall, compared to elderly women, who fall two to four times more often than men, are other important factors explaining the difference in the risk of hip fracture between men and women. The risk factor patterns in osteoporosis are also partly different in men and women (Jackson J 1997).

2.3.3. Race

The risk of hip fracture in white Caucasian women is reported to be twofold compared to black women (Farmer et al. 1984). Cancellous bone density increases during a relatively short period in late puberty more in black women than in white women, and the authors conclude that metabolic and hormonal events related to the achievement of sexual maturity during adolescence may be important determinants of the racial differences in bone mass in women (Gilsanz et al. 1991). Body weight might also explain partly the lower incidence of hip fractures in black women than in white women, as the prevalence of obesity is higher in the older black female population (Pruzansky et al. 1989). Hip axis lengths vary between Caucasians, African-American and Asian women, with African and Asian women having significantly shorter hip axis lengths than their Caucasian counterparts, which may diminish the risk of hip fracture in African-American and Asian women and the possible ethnic differences in geometry are postulated to be due to genetic and/or nutritional differences (Cummings et al. 1994, Theobald et al. 1998). However, there are also controversial findings concerning the hip geometry and the risk of hip fracture between the different ethnic groups (Chin et al. 1997).

2.3.4. Anthropometric factors

Anthropometric factors may have an influence on the occurrence of hip fractures (Farmer et al. 1989). Maternal height and a slow rate of childhood growth are major determinants of the subsequent hip fracture risk according to a longitudinal study. Whether a reduced growth rate is a consequence of childhood lifestyle, genetic background or intrauterine hormonal programming remains unknown (Cooper et al. 2001). Tall individuals have been observed to have a higher risk of hip fracture than short individuals in many studies (Hemenway et al. 1995, Lau et al. 2001), although opposite findings have been also reported (Huopio et al. 2000). Height may contribute to the risk of hip fracture by increasing the force associated with falling (Hayes et al. 1993) and height may also influence the geometrical proportions of the hip, such as the hip axis length (Faulkner et al. 1993) or the femoral neck length (Nakamura et al. 1994). Low weight has been reported to be an independent predictor of hip fracture (McGrother et al. 2002). Low weight is also a powerful predictor of very low BMD (T-score ≤ −3.5), which might explain the high risk of hip fracture and another possible explanation for the high risk of hip fracture in low-weight individuals is that a low body weight may be a general marker of poor health and frailty (Dargent-Molina et al. 2000). Low body mass index (BMI) has been established as a risk factor for hip fracture (Hemenway et al. 1988), because low BMI is related to low bone mass (Edelstein & Barrett-Connor 1993).

2.3.5. Bone mineral density

Many studies have shown that low bone mineral density (BMD) or low bone mass in the hip region is associated with hip fractures in women and may predict a future hip fracture risk (Libanati et al. 1992, Marshall et al. 1996). Each SD decrease in femoral neck bone density increased the age-adjusted risk of hip fracture 2.6-fold, and in the lowest quartile of BMD the risk of hip fracture was 8.5-fold in a cohort study (Cummings et al. 1993). There are fewer studies on men, but one study showed that men had OR 1.98 for a non-traumatic fracture risk, including hip fracture, compared to women with OR 2.39 based on the measurement of femoral neck bone mineral density (Nguyen et al. 1993). Peak adult bone mass is attained in early adulthood after the end of linear skeletal growth, and it is influenced by genetic factors, hormones, nutrition and physical activity (Stevenson et al. 1989, Tylavsky et al. 1989). Thereafter, there is a period of bone loss, which is associated with age, menopause and various risk factors, such as low body weight, alcohol use and smoking, nulliparity and lack of regular exercise (Stevenson et al. 1989).

2.3.6. Geometry

The geometry of the hip may be an important predictor of a future fracture, because the strength of an object is also a function of its geometry according to the basic engineering principles (Karlsson et al. 1996). Other important principles are the mechanical properties of the material from which the structure is made and the location and direction of the loads to which the structure is subjected in service (Mow & Hayes 1991). Torsional strain on a loaded femur will cause it to break at its weakest point, which is the more horizontal femoral neck. This was first pointed out in case histories by Sir Astley Cooper over 150 years ago (Parker et al. 1997). Since then, the upper femoral skeletal geometry has been presented to contribute to the hip fracture risk in dual-energy X-ray absorptiometry and conventional pelvic radiography studies but the results have been partly conflicting (Faulkner et al. 1993, Glüer et al. 1994, Karlsson et al. 1996, Dretakis et al. 1999, Michelotti & Clark 1999, Alonso et al. 2000).

2.3.7. Fall

Over 90% of hip fractures are due to a fall (Grisso et al. 1991), but only about 1% of all falls of the elderly results in a hip fracture (Tinetti et al. 1988, Nevitt et al. 1991). A comparison between the predictions of the impact force of falling and the in vitro measures of femoral fracture strength postulates that any fall from standing height producing a direct, lateral impact on the greater trochanter may break the elderly hip, (Robinovitch et al. 1991) and the influence of the direction of falling on the fracture risk has also been proven in a clinical series (Greenspan et al. 1998, Parkkari et al. 1999).

The tendency of the elderly to fall is high, which may partly explain the dramatic age-related rise in the incidence of hip fractures (Hayes et al. 1993). Established factors for an increased risk of falls are a slower hand reaction time, decreased grip strength, falls while using stairs and steps, turning around or reaching (Nevitt et al. 1991), cognitive impairment (at least five errors on the short portable mental status questionnaire), disability of the lower extremities (problems with strength, sensation or balance), use of sedatives (benzodiazepines, phenotiazines and antidepressants), foot problems (moderate or severe bunions, toe deformities, ulcers or deformed nails) (Tinetti et al. 1988), neuromuscular impairments (inability to walk in a line with feet in a tandem position and by a slower walking speed), visual acuity (Cummings et al. 1995, Dargent-Molina et al. 1996) and overall impaired mobility (Greenspan et al. 1998). For recurrent non-syncopal falls, increased risk ratios have reported for persons who have difficulty standing up from a chair, difficulty performing tandem walk (heel to toe), arthritis, Parkinson´s disease, three or more falls during the previous year and a fall with injury during the previous year and for whites (Nevitt et al. 1989). Alcohol intake and physical factors in the environment, such as stairs, lighting and streets and walkways, have also been cited as important factors (Gregg et al. 2000).

2.3.8. Lifestyle factors

The lifestyle factors having an influence on the occurrence of hip fracture are described in table 1.

Physical activity in childhood and adolescence improves bone strength, while activity in adulthood seems merely to reduce bone loss (Frost 1999). Stair climbing and brisk walking are associated with increased bone mineral density at the hip and in the whole body in postmenopausal women (Coupland et al. 1999). One study indicated that women who could go out with walking did not have an increased risk of hip fracture and those who had to stay at home and use a gait aid had a 2-fold risk. The authors postulated that those who could go outside had greater muscle strength and better neuromuscular function, stability and visual acuity, which reduced their propensity to fall (Boonyaratavej et al. 2001). No load-bearing activity in the immediate past and no vigorous sport activities in early adulthood resulted in RRs for hip fracture 2.0 and 7.2, respectively, for women in the Asian Osteoporosis Study (Lau et al. 2001). A lack of physical activity has also been found to associate with the risk of hip fracture in European women (Johnell et al. 1995).

A high-magnesium diet in postmenopausal women has been found to increase urinary calcium excretion, and this may explain the increased risk of hip fracture (Nielsen 1990). High intake of iron was also related to an increased risk of hip fracture according to one study, but the mechanism was uncertain (Michaelsson et al. 1995). High intake of vitamin C might cause negative calcium balance (Allen 1982) and may reduce cancelleous and cortical bone (Thornton 1970) . Nondairy animal foods (meat, fish, and eggs) are low in calcium and high protein/low calcium may be harmful to skeletal health and may increase hip fracture risk (Meyer et al. 1997). An inverse relation between coffee intake and bone mass has been observed, which is due to the calciuric effect of caffeine, which may thus increase the hip fracture risk (Hasling et al. 1992). An increase in bone mass caused by fluoride may be associated with an increase in bone fragility (Lindsay 1990). The reported influence of the fluoridation of drinking water on the hip fracture risk is controversial, and the differences between these studies might be due to different study designs (Sowers et al. 1991, Danielson et al. 1992, Cauley et al. 1995). Calcium intake declines with age, because of a decrease in the consumption of dairy products. The intestinal absorption of calcium also decreases with age because of the reduced ability of the intestine to adapt to a low calcium intake (Meunier 1996). The poor vitamin D status is mainly due to low exposure to sunshine not compensated for by vitamin D supplementation (Lips et al. 1987). Aging also decreases the capacity of human skin to produce previtamin D₃ (MacLaughlin & Holick 1985). The cumulative response to a deficit in calcium intake and a low vitamin D status is a negative calcium balance, which induces secondary hyperparathyroidism and increases the risk of hip fractures (Parfitt et al. 1982, Meunier 1996).

Smoking has been reported as a risk factor for hip fracture among postmenopausal women (Meyer et al. 1993, Law & Hackshaw 1997) and the risk was decreased after cessation (Baron et al. 2001). There is also a report showing no association between cigarette smoking and the hip fracture risk (Johnell et al. 1995). The possible mechanisms through which cigarette smoking could affect the fracture risk are the lower body weight of smokers and lower levels of parathyroid hormone and 25-hydroxyvitamin and lower BMD and BMI (Mellström et al. 1993).

Excessive alcohol use may play an important role in the pathogenesis of osteoporosis and increase the risk of hip fracture (Moniz 1994). On the other hand, social drinking is associated with higher bone mineral density in men and postmenopausal women. The beneficial effect on bone might be due to elevated serum estradiol levels (Holbrook & Barrett-Connor 1993). Any use of alcohol, however, seems to suppress the function of osteoblasts, as evidenced by the low serum levels of osteocalcin, and prolonged moderate drinking elevates the serum levels of vitamin D metabolites with consequent malabsorption of calcium, hypocalcemia and hypocalciuria (Laitinen & Valimäki 1991).

2.3.9. Medication and concurrent diseases

Several medications and concurrent diseases are associated with the risk of hip fracture and the previous literature is described in Table 2.

Sedative and autonomic effects of psychotropic drugs increase the risk of falling in the elderly (Ray et al. 1987) and may increase the risk of hip fracture (Cummings et al. 1995).

Thiazides may increase the bone mineral content in postmenopausal women (Wasnich et al. 1986), but the use of thiazides seemed not to decrease the risk of hip fracture or osteoporosis (Adland-Davenport et al. 1985). Furosemide is a diuretic agent that promotes calcium excretion by the kidney (Suki et al. 1970). It may expose users to an increased risk for osteoporosis and osteoporotic fractures (Tromp et al. 2000) by reducing BMD (Ooms et al. 1993). On the other hand, thiazides and furosemide may increase the risk for syncope, producing a possible mechanism of action for the noted association between the use of diuretics and hip fracture (Heidrich et al. 1991).

The use of oral corticosteroids has been established as an independent risk factor for hip fracture (RR = 2.1) (Baltzan et al. 1999) and for both nonvertebral fracture (RR = 1.44) and vertebral fracture (RR = 2.83) (van Staa et al. 2000). In the study by van Staa et al. (2000), a strong correlation was observed between the daily corticosteroid dose, rather than the cumulative dose, and the risk of fracture, with a higher risk in people using higher doses.

A weak relationship between the risk of hip fracture and cardiovascular diseases been reported earlier. The relationship was more prominent in women than in men (Lau et al. 2001).

Some new prospective studies have reported an increased risk of hip fracture in patients with diabetes. According to these studies, the relative risk of hip fracture was 6.9 in Type I (insulin dependent) diabetes (Forsén et al. 1999) and 1.8 in Type II (non-insulin-dependent) diabetes (Schwartz et al. 2001). The increased fracture risk could be due to altered bone status or complications of diabetes predisposing to trauma (e.g. retinopathy, peripheral neuropathy) (Meyer et al. 1993).

A history of stroke has been found as a risk factor for hip fracture (Ramnemark et al. 1998, Lau et al. 2001). The risk of hip fracture increases over 7-fold after hospitalization for stroke (Kanis et al. 2001). Hip fractures might be caused by the high incidence of accidental falls in stroke patients (Forster & Young 1995). Muscle weakness and an increased risk of developing osteoporosis on the paralyzed side might be other important factor predisposing to fractures in stroke patients (Hamdy et al. 1993).

The risk of hip fracture among patients with Parkinson´s disease was observed to be high in elderly women, and they had decreased BMI, lower BMD, and lower concentrations of serum ionized calcium and 25(OH)D with compensatory hyperparathyroidism (Sato et al. 2001). The increased risk of hip fracture in patients with Parkinson´s disease is probably due to their tendency to fall in specific ways (Johnell et al. 1992).

The frequency of hyperthyroidism has been suggested to be 2.5-fold in hip fracture patients compared to controls (Wejda et al. 1995). The increased risk of hip fracture associated with hyperthyroidism was not found in another study, and women with a history of hyperthyroidism and the use of thyroid hormone for a variety of thyroid disorders did not appear to have an enhanced prevalence of hip fracture (Solomon et al. 1993).

2.3.10. Gynaecological factors

Postmenopausal women with undetectable serum estradiol concentrations and high serum concentrations of sex hormone-binding globulin appear to have an increased risk of hip and vertebral fracture (Cummings et al. 1998). Estrogen deficiency results from declining ovarian function (Thomsen et al. 1986). The estrogen deficiency and bone loss might be caused by the higher prevalence of dead osteocytes (Tomkinson et al. 1997).

Bone turnover is altered during pregnancy and lactation, as demonstrated by a change in the markers of bone formation and resorption (Sowers 1996) and, in the case of lactation, even with measurement of bone mineral density (Holmberg-Marttila & Sievänen 1999). Despite this turnover activity, there appears to be little ultimate loss of mineral from the maternal skeleton during the pregnancy or lactation of well-nourished women if, during or after lactation, consistent menstrual cycling is re-established within a reasonable length of time (Sowers 1996). The actual net long-term effect of parity and lactation on the osteoporotic fracture risk is uncertain. Higher parity might be modestly associated with a reduced hip fracture risk, and this risk reduction seems partially attributable to weight gain with parity. According to the same authors, lactation is not associated with the hip fracture risk (Michaëlsson et al. 2001).