CHAPTER 1
An Overview of Osteoporosis
DAVID M. REID
Professor of Rheumatology, University of Aberdeen, Department of Medicine and Therapeutics, Medical School, Foresterhill, Aberdeen, AB25 2ZD, UK, Email: d.m.reid@abdn.ac.uk
Key Points
• Osteoporosis is a systemic skeletal disease with loss of bone mineral leading to excess fracture risk
• The diagnosis of osteoporosis is based on measurements of axial bone mineral density, but there are a number of other techniques which also predict future fracture
• Cost-effective intervention with pharmaceutical preparations is based on the diagnosis of osteoporosis, but in addition increasingly there is a need to consider the absolute fracture risk
• Nutritional and other non-pharmaceutical measures may be a useful and potentially cost-effective adjunct to pharmaceutical treatments or an alternative preventative measure
• More research is required to determine the appropriate targets for pharmaceutical and particularly nutritional interventions
Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality, a somewhat nebulous concept, which includes the biochemical integrity of bone. While fractures of the vertebral body, distal forearm (Colles) and proximal femur are considered to be characteristic, it is important to realize that not all fractures of these bone sites are due to osteoporosis and low trauma fractures of most skeletal sites, except arguably the ankle, can be associated with low bone mass.
As not all fractures of even classical sites are associated with low bone mass, it is important to have a practical definition, which can be used in vivo. Architectural features of bone can only be assessed in vitro by three-dimensional computed tomography (CT) techniques and by scanning electron micrographs, which demonstrate marked differences in the trabecular structure of cancellous bone in normal and osteoporotic subjects (Figure 1.1).
However, such three-dimensional techniques cannot yet be used in vivo and accordingly a working group of the World Health Organization (WHO) has defined osteopenia and osteoporosis according to what can be measured, that is bone mineral content (BMC) or bone mineral density (BMD) (Table 1.1).
Use of this definition has allowed the prevalence of osteoporosis at different skeletal sites to be determined for women in the Western world (Table 1.2) and these prevalence figures are roughly equivalent to the prevalence rates of hip and other fractures at various ages (see Chapter 3).
The term 'osteopenia' as used by the WHO can be confused with radiological osteopenia, that is bones which appear demineralized on X-ray. As the BMC/ BMD term 'osteopenia' has not subsequently been found to have clinical relevance, it has been largely ignored of late. The WHO definition only applies to women, although recent reviews have suggested that applying the same definition to men based on a male normative range would have the same utility, although this is not universally accepted.
The need for a diagnosis to be based on the assessment of BMC or BMD has encouraged further development of bone mass measurement tools of which there are now a confusing profusion.
Measurement of Bone Mass
In the last four decades, there has been an increasing interest in capturing numerically the obvious appearance of bone demineralization (loss of bone mineral), which may be an inevitable accompaniment of ageing of the skeleton. This interest was initially spurned by the observation that there could be up to 30% reduction in bone mass before it became radiologically evident. This headlong rush to develop new techniques has been given impetus by the decision by the WHO working group to define osteoporosis by BMC or density (see above). The various techniques, which are still in use in some guise in the new millennium, are summarized in Table 1.3.
Initially, techniques used simple measures of cortical thickness (radiogrammetry) measured laboriously and imprecisely from radiographs using a ruler and Vernier calipers. However the field was revolutionized in the 1960s when Sorenson and Cameron first described the use of photon absorptiometry to measure BMC of the forearm. The physics of the various techniques described since the initial observations are beyond the scope of this chapter, but photon absorptiometry has become the standard technique of assessment today with the initial radioisotope sources used to produce photons being replaced with much more stable and reproducible X-ray sources. Peripheral BMC, usually assessed at the radius or os calcis was measured initially using the absorption of transmitted photons from a single energy iodine source (SPA). However, use of a single photon source required the measurement to be carried out while the limb was immersed in water, which acted as a soft tissue equivalent thus allowing the transmission profile of water/soft tissue to be compared with significantly more dense bone.
The use of a water bath is somewhat inconvenient for peripheral bone sites and impossible for axial sites hence encouraging the development of 'dry systems', which currently use a 2-photon energy system replacing the original isotope photon source with X-rays, viz. dual energy X-ray absorptiometry (DEXA or DXA). This has become the standard clinical methodology for peripheral and axial measurements allowing assessment of areal BMD (BMC corrected for the assessed bone area) at sites of importance for fracture, including the forearm, lumbar spine and both proximal femurs (Figure 1.2).
The DEXA techniques thus allow a measurement of the mineral content of bone partially corrected for skeletal size, albeit only in two-dimensions. Accordingly, many authors have criticized the use of the term 'BMD' as assessed by DEXA as misleading, because it can only be considered to be areal BMD and incompletely corrects skeletal dimensions. Use of additional correction equations to determine estimated volumetric BMD have been published and have value, but it must be remembered that one of the main purposes of measurement of bone mass is in fracture prediction and here the data support the use of areal BMD as the preferred measurement. Assessment of true volumetric bone density is possible using CT technology; this technique has the disadvantage of requiring very expensive CT scanners and also involving high radiation exposure at least when used at axial sites. However, it has the advantage of being able to assess both cortical and trabecular bone either at peripheral sites, usually the radius, or at the important axial sites, most commonly the vertebral bodies.
For peripheral bone measurements, a new development has been the use of a non-ionizing radiation method, quantitative ultrasound (QUS). As can be seen from Table 1.3, this uses either transmission of propagated ultrasound through a peripheral bone or reflection of the ultrasound wave from primarily cortical bone. Transmission QUS allows measurements of attenuation of the broadband ultrasound beam and the speed of passage of the sound-wave across the bone along with manufacturer specific combined indices such as the inappropriately named 'stiffness', which is little to do with the elasticity of bone. Such indices correlate rather poorly in vivo with site-specific and distant-site BMD measurements, implying that the measurement is assessing other bone parameters as well as BMC and density. As QUS techniques do not measure bone density directly, they cannot be used to diagnose osteoporosis, as the definition of the condition is firmly dependent on the assessment of BMC or density. They do, however, predict those patients who subsequently fracture almost as well as BMD measurements and may give additional data on bone structure, a parameter poorly captured by the current methods of BMD measurement An important potential use of bone mass equipment for the nutritionist is the assessment of body composition. Whole body DXA techniques allow measurement of bone and soft tissue using the two energies of X-rays assessed as part of the measurement protocol. Software splits the measurement of soft tissue into three compartments, viz., (1) bone, (2) lean body mass and (3) total body fat, although to derive data for a three-compartment model accurately, it would theoretically be important to have beams of three different energies rather than two. For this reason, the technique has not received very wide-spread use and while giving some useful and fairly reproducible data, different machines may give markedly different values.
In summary, measurement of bone mass can be used theoretically to address the questions laid out in Table 1.4.
The requirement to use various techniques for diagnosing osteoporosis based on BMC or density clearly rules out the use of QUS or possibly radiogrammetry as potential diagnostic tools, but the more important question is whether the techniques predict future fracture. If, as seems likely, the diagnosis of osteoporosis and particularly intervention thresholds in the future becomes more allied to life-time or 10-year fracture risk, then clearly as all techniques predict fracture, all will have future utility in diagnostic terms. It does not seem to matter at which site bone mass is assessed in terms of fracture prediction although site-specific assessment does show a slightly improved relative risk of future fracture compared with distant site assessment (Table 1.5).
Intervention Thresholds
In recent years, decisions on treatment with pharmaceutical preparations have become dependent on the presence of a diagnosis of osteoporosis, i.e. an axial BMD measurement below a T-score of (2.5. However, the publication of 10-year absolute fracture risks for men and women have shown that these are dependent not only on age as discussed in Chapter 2, but also on BMD and sex. As can be seen from Figure 1.3, rates of fracture in women at any age are much higher than in men, but of more significance in terms of cost effective pharmaceutical intervention, the absolute risk of fracture at any one age in either sex is heavily dependent on the BMD measurement. This means that intervention with an expensive preparation is unlikely to become cost effective in younger post-menopausal women or middle-aged men unless they have incredibly low BMD values. If nutrition and other lifestyle changes can be shown to be effective in fracture prevention (see Chapters 29 and 30) and such interventions turn out to be less expensive than the newer pharmaceutical preparations, then it may be that such preventative treatment could be targeted at younger middle-aged subjects of either sex.
Until cost effective intervention thresholds based on absolute fracture risk predictions are developed for each therapeutic intervention, the over-riding question is whether intervening at a particular bone threshold, for example a T-score of < – 2.5, measured at a specific site, such as the total femur will be associated with fracture reduction. This has only been demonstrated with axial BMD and then only with the bisphosphonates. Until such data become available with other intervention thresholds it is dangerous to assume that treating women with low QUS scores, for example, will necessarily translate into absolute fracture reduction. For that, if no other reason, recent guidelines have suggested that 2-site axial DEXA (usually spine and hip) is the current method of choice for diagnosis. Targeting BMD on those with risk factors has been suggested by recent guidelines (Table 1.6), an approach recently endorsed by a meta-analysis of the literature.
Many of these risk factors are historical and not necessarily evidence-based, but act as the best decision process available for case-finding, reflecting as they do many non-nutritional risk factors for osteoporosis (see Chapter 4). Although genetic factors are clearly the most determinant of bone mass (see Chapter 5), only a maternal hip fracture is accepted as an indication for BMD, reflecting the difficulty of clinically defining the condition of osteoporosis without bone mass assessment. As yet there are no cost-effective data available, which would argue in favour of population screening at any age, although guidelines in the US do consider that assessment and treatment of all women over the age of 60 could be cost-effective, if a cost per quality associated life year of $30 000 is accepted. As the costs of the management of current fractures in the UK has been estimated at £1.7 billion per annum, the potential saving that could be induced by a population-based approach to fracture reduction including targeted assessment of bone mass is likely to be considered in future years. What is universally accepted is that BMD measurements are not simple to interpret and require an experienced operator.
Targeting Prevention without Bone Mineral Measurements
As indicated above, it appears that for cost-effective use of bisphosphonates to prevent fracture, targeting treatment based on measurements of axial DEXA are essential. However, other therapies such as hormone replacement therapy may be effective in women regardless of their BMD. As will be discussed in Chapter 8.2, calcium may have a role in fracture prevention regardless of the presence of osteoporosis, especially in the elderly and when used in association with vitamin D (Chapter 9). Such therapies may not to be targeted at those specifically with low bone mass. For example, calcium and vitamin D are recommended in fracture prevention in the frail elderly especially those at risk of hip fracture. Recent evidence suggests that vitamin D supplementation may improve muscle strength and hence potentially reduce falls in those who are deficient. Therefore, it may be concluded that vitamin D supplementation will in the future need to be targeted at those who have been shown to be deficient. Similarly, wearing hip protectors may prevent hip fractures and an obvious use may be to target the use of these garments in those at risk of hip fracture due to frequent falls.
Conclusions
This chapter has briefly reviewed the relationship between osteoporosis and fractures, the epidemiology of which is fully discussed in Chapter 2. While there are many techniques for measuring bone mass, only BMD measurements can be used to diagnose osteoporosis although other techniques are almost as predictive of fracture. Previously, intervention decisions have been based simply on a diagnosis of osteoporosis, but there is increasing recognition of the importance of the use of 10-year fracture risk to determine cost-effective intervention. The use of relatively expensive drug therapy may therefore require to be targeted at those with a high 10-year fracture risk including a diagnosis of osteoporosis. There is therefore a clear role for non-pharmaceutical interventions, such as nutrition in prevention and treatment in those at lower absolute risk. Further work is required to determine the most appropriate triggers for nutritional and other pharmaceutical interventions.
