We are all different: insights from osteoporosis research in Asia
: Swan Sim Yeap, Subang Jaya Medical Centre, 1, Jalan SS 12/1A, Subang Jaya, Selangor, 47500, Malaysia. Email: firstname.lastname@example.org
Osteoporosis only became a ‘disease’ entity in the 20th century. After the initial observations and definitions of osteoporosis based on Caucasian populations, systematic research in Asian populations started in the 1980s. Significant variations between different ethnic groups with respect to the rate of osteoporotic fractures, bone mineral density and disease risk factors emerged from the data; this article highlights some of the earlier important findings and the dissimilarities. Osteoporosis is therefore not a homogeneous disease across the world.
Osteoporosis was first described in the early 1800s when British and Irish surgeons recorded clinical descriptions of hip and wrist fractures.1 Astley Cooper, the British surgeon, observed in his book, A Treatize on Dislocation and on Fractures of the Joints, published in 1824, that ‘old age, is attended with changes . . . one of the principal of these is found in the bones, for they become thin in their shells and spongy in their texture’.2 However, the actual word ‘osteoporosis’ first appeared in French around 1820. A French pathologist, Jean Lobstein (who described Lobstein's disease or osteogenesis imperfect type I) coined the word ‘osteoporosis’ from the Greek word ‘osteon’ meaning lamellar or compact bone, to which he added ‘poros’ meaning pore or little hole. Thus ‘osteoporosis’ literally meant ‘porous bone’, describing the cavities that were observed by the pathologist in certain patients’ bones.3
Gustav Pommer, a German scientist, first established the difference between osteoporosis and osteomalacia in 1885. Pommer showed that rickets and osteomalacia represented a failure to mineralize new bone as it was being formed, leading ultimately to a calcium deficit in the bony tissue itself, whereas osteoporosis was a deficit of whole bone tissue without change in its mineral content.3
The next breakthrough came in the 20th century with the description of osteoporosis by Fuller Albright, the American endocrinologist. In his 1940 paper at the American Medical Association conference, Albright correctly defined the disease known as osteoporosis. He suggested there were three types: postmenopausal, senile and by disuse, and he indicated that treatment with oestrogens was the basis for prevention and treatment of osteoporosis.4 In the 1960s, Christopher Nordin from Australia started drawing attention to the role of calcium deficiency as a cause of osteoporosis.5 Thus the fundamentals of osteoporosis were set.
DEFINITION OF OSTEOPOROSIS
In the 1980s, various techniques became available to measure bone mass or density. Together with this ability, along the way, osteoporosis changed from a ‘condition’, that is, a state of thin bones, to that of a ‘disorder’, that is, a ‘derangement or abnormality of function’ and finally became a ‘disease’, that is, a definite morbid process having a characteristic train of symptoms.
In 1991, a Consensus Development Conference defined osteoporosis as a ‘systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture risk’.6 This definition was subsequently accepted by the World Health Organization (WHO) in 19947 and was widely used until a revision in 2000 which defined osteoporosis as a ‘skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture’.8 With these definitions came the classification of osteoporosis based on bone mineral density (BMD) measurements and the idea of a ‘fracture threshold’– a cut-off for BMD that captures most patients with osteoporotic fractures. Based on American White female data, the WHO took a value of BMD more than 2.5 standard deviations below the mean for healthy adult women at any site (spine, hip or mid-radius) as osteoporotic. This level identified 30% of all postmenopausal women as having osteoporosis, of which more than half would have sustained a previous osteoporotic fracture.7 However, such a definition of osteoporosis based on the normal distribution is not entirely satisfactory as it could change depending on the reference population used.
FRACTURE RATE DIFFERENCES
The end result of a low BMD is an osteoporotic fracture. Initial estimates of osteoporosis prevalence counted hip fractures as a marker, as subjects with these fractures inevitably present to the hospitals, making ascertainment of cases more straightforward. One of the earliest studies on hip fracture in Asia came from Singapore, showing an age-adjusted rate of hip fracture of 75/100,000 in women who were 60 years of age and older.9 In Hong Kong, between 1965–1967, the rate of hip fractures was 153/100,000 in women and 96/100,000 in men.10 Between 1988–1992, the hip fracture rate in Chinese in Beijing was 87/100,000 in women and 97/100,000 in men.11 In a 1987 Japanese study, the hip fracture rate was 220–260/100,000 in 70–74-year-old-women, rising to 1180–1390/100,000 in 85–59 years olds.12 Thus, hip fractures were less common in Asians compared to Caucasians; for example, in the Rochester (American) White population, the hip fracture rate was 510/100,000 in women and 174/100,000 in men between 1965–1974.13 Interestingly, even within the same country, the different races can have different rates of hip fracture. In Singapore, hip fracture rates were higher in the Chinese and Malay, compared to the Indian population.14
These differences were maintained in subsequent later studies done in the 1990s. A study comparing five different countries including Hong Kong and Beijing done in 1990–1992 showed the age-adjusted hip fracture rate in women and men over the age of 50 were highest in Reykjavik, Iceland, followed by Hong Kong, and then Beijing, China. The rates in the three countries were 697, 428 and 96 per 100,000 women, and 349, 270, 107 per 100,000 in men, respectively.15 The 1997 figures for hip fracture in three Asean countries confirmed the trend of lower hip fracture rates in Asia. In the age-adjusted hip fracture rates per 100,000 for women, there were 442 fractures in Singapore, 269 in Thailand and 218 in Malaysia. For men, the numbers were 164 in Singapore, 114 in Thailand and 88 in Malaysia.16 Again, these figures were much lower than the US White data from 1989 presented in that paper which showed a hip fracture rate of 535/100,000 for women and 187/100,000 for men.
What these later studies also showed was that the hip fracture incidence seemed to be rising and the suggestion was that hip fracture rates increased with increasing urbanization, but exactly why it should be so has not been easy to elucidate. Certainly in Hong Kong, where there was rapid urbanization, the incidence of hip fracture was doubled between 1966 and 1985.17 Similarly, in Singapore, the hip fracture rate in women increased 5-fold from the 1960s to 1990s.14
Vertebral fractures have not been so well studied in Asia, but the story is similar, albeit the differences are not so marked. Melton found that the prevalence of vertebral fractures in a population-based sample in Minnesota, USA was 11.7% in 60–64 years olds and 16.2% in 65–69 years olds.18 In Japan, the prevalence of vertebral fracture in a population-based sample was 5.7% in 60–64 years olds and 13.0% on 65–69 years olds.19 Another study found an increased odds ratio for prevalent vertebral fractures of 1.8 (95% CI 1.3–2.5) in native Japanese women compared to Japanese-American women.20 In the Chinese in Beijing, the age-standardized prevalence of vertebral fractures was 5.5% lower compared to women in Minnesota, USA.21
BONE DENSITY DIFFERENCES
One of the obvious possible reasons for this difference would be differences in BMD amongst the different ethnic groups. Beginning in the 1990s, publications on BMD in different populations began to appear. Surprisingly, although the fracture rate is lower in the Asian populations, these studies showed generally lower BMD in Asians compared to Caucasians.
One of the earlier studies published in 1994 showed lower BMD in Asian Indians living in London compared to Caucasians.22 When they corrected for skeletal area, the Asians had similar BMD at the lumbar spine, but the femoral neck difference persisted. Average BMD values of the lumbar spine in Japanese23 and Korean24 females are lower in the over 60 age group compared to American women. In Taiwan, lumbar spine BMD have similar values to European or American White populations, but hip BMD have lower values.25 Vietnamese, Cambodian and Loatian men and women were found to have lower BMD compared to Caucasians.26 After correcting for volumetric bone mineral apparent density, the femoral neck differences disappeared, but lumbar spine remained slightly lower.26 Comparison of BMD between Caucasians and Chinese show that osteopenic Chinese women have lower BMD than Caucasian women diagnosed with osteoporosis.27 For example, an osteopenic Chinese at T –2.0 would have a lumbar spine BMD of 0.890 g/cm2, compared to an osteoporotic Caucasian at T –2.5, with a lumbar spine BMD of 0.907 g/cm2. A similar over-estimation of the prevalence of osteoporosis was found when the Hong Kong Chinese BMD reference norms were produced.28
The lower BMD values may be due to a lower peak bone mass which has been found to be 5–15% lower in Chinese compared to that of Caucasians.27 The outcome of these studies led to the development of country and/or ethnic specific ‘normal’ ranges for BMD, which is now regarded as the standard practice.
AND FINALLY, WHAT ABOUT CALCIUM?
As the differences in BMD did not explain the differences in fracture rates, research moved onto studying the other risk factors, of which calcium was an obvious choice. Calcium intake in Asian populations is generally much lower than in Caucasians. A report by the Food And Agricultural Organization (FAO) stated that the average daily calcium intake in 1987–1989 in developing countries was 344 mg compared to 1031 mg in USA and Canada.29 These levels have increased slightly with increasing urbanization; in Hong Kong, the average daily calcium intake was 472 mg in a 1998study.30 More recently, in Malaysia, the average calcium intake was found to be 483 mg daily31 but in rural Thais, the daily intake is still extremely low, 266 mg in a recent study.32 However, within this low calcium intake, those who are at the lower end of the daily range are more at risk of hip fractures than those at the higher end.33 The importance of the other risk factors in the Asian population is in the process of being clarified, with on-going research.
Osteoporosis is not a homogenous disease throughout the world. As a result, these differences have led to many Asian countries in the mid-1990s to produce nation-specific osteoporosis guidelines which would be useful in the local context. Some of the countries that have local guidelines available include Australia, Hong Kong, Japan, Malaysia, New Zealand and Singapore.
In conclusion, there are intrinsic ethnic differences in osteoporosis epidemiology in different populations which should be taken into account in any discussion of the condition.