What-isL.QsteQPQrQ?i§ %
Osteoporosis is a generic term used to describe a specific form of osteopenia, which may be defined as a deficiency of calcified bone (Bauer, 1960). Osteopenia is not a recently recognised phenomenon. Almost 150 years ago it was noted that 'the bones of aged people not infrequently become extremely light and spongy, readily break, and from the diminished amount of compact tissues may in the case of the flat bones such as the pelvis, be indented by firm pressure with the finger' (Tomes & De Morgan, 1853). However osteopenia requires further differentiation for effective diagnosis and treatment Despite first being differentiated over 100 years ago (Pommer, 1885), the two most common adult osteopenic conditions, osteoporosis and osteomalacia are commonly confused. While osteoporosis is characterised by a decreased density of normally mineralised matrix, osteomalacia is a condition of insufficient mineralised bone matrix (see Fig 4.16 & 4.17).
The classical deBnition of osteoporosis was made in 1948 by Albright and Reifenstein who described the condition as of one of too little bone in the bone'. While osteoporosis is therefore characterised by low bone density, the composition of the remaining bone is normal. The current World Health Organisation (WHO) definition of osteoporosis is: 'A
disease characterised by low bone mass and micro-architectural deterioration o f bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk' (WHO Study Group, 1994). The concept of deteriorating bone micro-architecture is an important one.
While osteoporosis is primarily a disease of loss of bone mineral density, this alone is often not enough to explain the fractures which occur. However while the assessment of such micro-architectural damage is unable to be assessed, measurements o f bone mineral density may be readily made.
The WHO sub-divides osteoporosis into two classes depending on the severity o f osteopenia. When assessed in terms of bone mineral density (BMD) or bone mineral content (BMC) individuals with values between 1.0 and 2.5 standard deviations (SD)
Normal Bone
O steoporotic Bone B on e mass decreased M ineralisation normal
Osteomalacic Bone
Bone mass variable (most commonly decreased) Mineralisation decreased
H Unmineralised matrix
M l Mineralised matrix
Figure 4.17: The differentiation of osteopenia. Comparison o f bone mass and degree of bone mineralisation in osteoporotic and osteomalacic bone.
below the sex-matched young adult mean are described as having osteopenia, while those having BMD and BMC values 2.5 SD or more below the young adult mean are considered to be suffering from osteoporosis (Barlow, 1994). It has also been proposed that a further category, that of severe osteoporosis be established for those individuals
with a BMD or BMC more than 2.5 SD below the young adult mean value in the presence of one or more fragility fractures (Kanis et al.^ 1994). The risk of fragility fractures increases with declining BMD (Hui et a i, 1988; Melton et al., 1993), with an estimated 1.5 to 3-fold increase in fracture risk for each decrease in BMD representing one standard deviation (SD) of the mean population value (Kanis et at., 1994). Comparing the measured BMD with the sex-matched young adult mean BMD gives a value known as the T-score*, which has replaced comparisons with sex and age-matched reference means (Z-score). This is because even though fracture risk increases with age in response to decreasing BMD, the overall incidence of osteoporosis as identified by Z- score remains unchanged. Using definitions based on T-scores means the prevalence of osteoporosis in females increases almost exponentially with age after 50 years, a pattern which more accurately reflects the clinical presentation of these patients (Kanis et at.,
1994).
The Epidemiology of Osteoporosis
Bone fractures are most common in the young and the elderly. While long bone fractures predominate in the young, in those above the age of 45 years fractures of the hip, spine and wrist predominate (Melton, 1988). These are the classic fractures of osteoporosis. The characteristics of these fractures were recognised over a century ago (Cooper, 1824). Fracture incidence increases with age, is higher in females and may be associated with only moderate trauma at sites containing large amounts of trabecular bone.
The estimation of the number of individuals suffering from osteoporosis is difficult, and it is not possible to estimate the total number of whole body fractures that are caused by osteoporosis (Barlow, 1994). Problems in identifying the frequency of vertebral fracture and its attendant morbidity have also been reported (Kanis & McCloskey, 1992; Kanis & the WHO Study Group 1994; Melton et a l, 1993). However, the estimated cost of hip fractures, (the most severe fracture characteristic of osteoporosis) in England alone was £742 million in1992/93 (Cooper & Jones, 1993). Estimates of the incidence of osteoporosis in the US have varied widely, ranging between 15 and 20 million (Benger et at., 1988; Melton et a l, 1989; Norris, 1992), with a current annual cost to the US healthcare system of $10 billion (Mundy, 1995). The most recent estimates of osteoporosis using the WHO definitions suggest a likely incidence of 30% in UK and US Caucasian women (Kanis et a l, 1994; Melton et a i, 1989). The degree of morbidity and mortality associated with osteoporotic fracture is not disputed (Silverman, 1992). Demographic changes will cause a further increase in the incidence of these fractures over the next sixty years (Barlow, 1994).
Women are at particular risk of fracture due to lower peak bone mass, accelerated bone loss at the menopause, a greater likelihood of falls and a significantly greater longevity
than men (Hansen et a i, 1991). These factors combine to mean that women account for 75% of osteoporotic fractures in most Western counties. At the menopause Caucasian women face a remaining lifetime fracture risk of between 30 and 40% (Kanis & the WHO Study Group, 1994).
The use of BMD measurements to aid the understanding of osteoporosis led to the concept of the "fracture threshold". This represents a theoretical point below which patients will suffer an osteoporotic fracture. Such approaches suffered from the arbitrary setting of the threshold which lacks either sensitivity or specifîcity, depending on the value selected. Furthermore the imposition of a single cut-off limit ignores the fact that risk of fracture increases continuously with decreasing BMD and does not alter in a quantum fashion (Kanis et aly 1994).
W hy does Osteoporosis O ccur ?
Fractures occur due to a mechanical imbalance between bone strength and any force applied to i t Bone mass and therefore bone density in later life, depend on the peak bone mass achieved on cessation of linear growth and the subsequent bone loss.
Environmental factors such as calcium intake and physical activity interact with genetic influences to determine the peak bone mass of an individual (Johnston et aly 1992). In girls, the age of onset of puberty is also thought to play a role (Johnson & Slemenda,
1994). In pre-menopausal females, the gonadal hormone oestrogen is known to be a major factor in the maintenance of bone mass. Indeed the most established treatment (and prophylactic therapy), against osteoporosis related to artificial w natural menopause is the replacement of lost oestrogeiL This is known as hormone replacement therapy (HRT). A number of risk factors for osteoporosis have been identified. These include: family history, white race, small stature, female gender, early menopause, late menarche, low dietary calcium, sedentary life style, smoking, drug-use. Another major cause of osteoporosis, especially in younger subjects is related to the use of corticosteroid drugs. Steroids inhibit bone formation while reducing intestinal calcium absorption and
increasing urinary calcium reabsorption. Com pensatory (secondary)
hyperparathyroidism and increased bone resorption follow (Hahn, 1993). While reduction of corticosteroid dose removes the cause of the osteoporosis, this may not be possible in all cases. In such situations the use of anti-resorptive agents such as the bisphosphonates have proved effective (Reid et a l y 1988).
Although of much lower incidence than in women, osteoporosis does occur in men, often related to hypogonadism. Once all other causes (endocrinopathies, osteomalacia, drug- induced e t c . ) y have been excluded, a diagnosis of idiopathic osteoporosis may be made (Jackson & Kleerdcoper, 1990). While secondary osteoporosis is most readily combated
by the treatment of the underlying disorder, the treatment of idiopathic male osteoporosis is not well established. This may be due to a possible heterogeneity of bone metabolism in this condition, with sub-groups of low bone formation and increased bone turnover (Perry e ta/., 1984). The possibility of two such distinct groups has also been postulated to occur within post-menopausal osteoporosis (Arlot e t a/., 1990). This supposition is supported by wide variations in biochemical markers of bone turnover such as osteocalcin, which has been variously reported as low, normal and high in post menopausal osteoporosis (Brown e t a i , 1984; Duda e t a L y 1988; Ismail e t al.y 1986). This heterogeneity occurs within post-menopausal osteoporosis (Type I osteoporosis) and should not be confused with the delineation of this condition from age-related (type U osteoporosis) (Riggs & Melton, 1983). While biochemical markers of bone metabolism have been successfully used in predicting bone loss and response to treatment (Christiansen e t a l y 1987; Gamero e t a l y 1994a), it may be that different sub-groups and
types of osteoporosis may exhibit a range of responses to different modes of therapy. The assessment of bone turnover, possibly using biochemical markers of bone metabolism may have a role in choosing the optimal therapy in an individual patient