International Conference on Osteoporosis Being Held

The International Conference on Osteoporosis Being Held in Kobe
The International Conference on Osteoporosis now being held in Kobe has attracted more than 700 participants, including about 500 Japanese and 200 others from 30 countries around the world. The conference opened on the morning of Nov. 5 (Tuesday), 1001, and continues through today, Thursday, Nov. 7, at the Kobe Portopia Hotel in Minatojima Nakamachi on Port Island in Kobe.
The conference officially got underway Tuesday morning with opening remarks by Secretary General Masaaki Fukase who thanked participants for attending the conference. Chairman Takuo Fujita then spoke on the importance of this conference, the first of its kind ever held in Asia. This was followed by the reading of a congratulatory message sent by Hisashi Teramatsu, who is the director general of the health service bureau of the Ministry of Health and Welfare. Delivering the keynote address for the conference was Honorary President Dr. B.E.C. Nordin.
Various study sessions were held during the three-day period. Those covering progress in the field until now included: Epidemiology of Osteoporosis, Risk Factors and Life Style, Peak Bone Mass and Whole Body Composition, Diagnosis and Identification of Subjects at Risk, Bone and Biochemical Measurements, Pathogenesis: Cytokines and Immunity, and Pathogenesis: Bone Cells, Hormones, and Growth Factors. There were also several sessions dealing with future trends, including: Prevention: Estrogen, Calcium, and Exercise, Treatment: Vitamin D Metabolites, Treatment: PTH and Calcitonin, and Treatment: Fluoride, Bisphosphonates, Anabolic Steroids, and New Developments.
Within the time frame of the International Conference on Osteoporosis several related symposia and sessions were also being held. The satellite symposium Methodologies for Bone Mineral Assessment takes place on Nov. 8 and 9 in Nara City at the Nara Ken Public Hall.
Also, a special session called Calcium Supplements: Present and Future, Experience with AA Calcium and AAA Calcium was held Monday under the leadership of Dr. T. Fujita. On Tuesday, a session entitled Bone Pain and Analgesic Effect of Calcitonin was held with Drs. H. Morii and H. Kawashima presiding. Recent Studies of the Use of Dexa also with R. Morita.
Another related session, The 5th Bone Forum, will take place at the Hotel New Otani in Osaka on Friday and in Tokyo on Saturday under the leadership of Drs. K. Kurokawa and Y. Seino.

Rapid Progress in Concept of Disease
By Takuo Fujita
Chairman, Local Organizing Committee, International Conference on Osteoporosis
Welcome to the International Conference on Osteoporosis! Due to the aging of the population starting from the industrialized nations of the world and gradually involving every country across the globe, osteoporosis is constantly increasing to become a definite threat to the health, welfare and economy of each nation. It is already the most widespread disease of mankind and will no doubt keep increasing unless we do something about it. It is therefore quite urgent for us to concentrate our efforts toward understanding the nature, prevalence, consequences and complications of the disease for effective prevention and treatment. Osteoporosis is a complex and multifactorial disease with different manifestations at each age, between males and females and among different parts of the world. It takes investigators from many fields under international cooperation to draw a complete picture.
Black people have more bone and sustain fewer fractures than white. Asians have less bone, probably more vertebral fractures but less hip fractures than Caucasians. In addition to genetic factors, differences in lifestyle and nutritional intake and influences according to industrialization are probably responsible for such differences.
It took many centuries for science to focus its attention on osteoporosis. This is the 50th year of the publication of Albright's epoch-making paper establishing osteoporosis as an independent disease. The concept of osteoporosis, its pathophysiological understanding and diagnostic technique such as bone measurement has made extremely rapid progress over the years. Many of the distinguished investigators who contributed to such progress are here today, and we are honored to welcome them.
In addition to the fruits of active scientific discussion, renewal of friendship and impression of the city of Kobe in the fall, I hope you will learn something beneficial to take home with you.
In view if the higher complications of osteoporosis such as hip fractures in North America and Europe than in Asia, the model of living in Asia with more strain on the hip musculature may be contributing to the lower fracture rate.
It may be worthwhile to consider adjusting our lifestyle to minimize the complication of osteoporosis. Finally, it is my pleasure to announce the inauguration of the Japan Osteoporosis Foundation today. We are happy to join the World Federation of Osteoporosis Foundations, Needless to say, the support of the general public is quite important for progress in osteoporosis research and its application to achieve the welfare of mankind.

Keynote Paper on Bone Density
Professor Christopher Nordin presented the keynote paper on Bone Density, Bone Loss and Fractures. He showed to begin with that bone density was more important than bone mass in determining fracture risk.
The popular view that small stature predisposed to osteoporosis was therefore incorrect. In young adults, bone size and bone mass were related, but with advancing age and in osteoporosis subjects this relationship was lost, indicating that women do not lose bone in parallel but at greatly different rates.
In a five-year study of over 300 women, the rates of loss varied by a factor of 5. This meant that the midlife bone density (often called peak bone density) was much less important in the pathogenesis of spine and hip fractures than was generally assumed.
Initial bone density was the main determinant of bone density for about five years, but alter that differences in rates of loss became progressively more important and ultimately dominant. Although Professor Nordin was a strong advocate of bone density screening at middle life, for which he considered forearm densitometry perfectly adequate, he has reached the conclusion that such screening would need to be repeated approximately every five years.
Although it was impossible to define the constancy of bone loss in any individual over a long period, the makers of bone turnover were remarkably constant over a five-year period.
Women with the highest bone turnover at the beginning of the five-year period were generally those with the highest turnover at the end of the period and it seemed likely that, without intervention, those who lost most rapidly in the initial stages of aging would continue to be the faster losers in the future.
He was not able to identify a subpopulation of "fast bone losers" but simply observed that some apparently normal women lost bone faster than others.
He then turned to the most important osteoporotic fracture syndromes - fractures of the spine and fractures of the hip. He considered that both were more die to rapid bone loss than to low initial bone density.
In vertebral crush fracture cases, he presented evidence that these patients as a group suffered from two important physiological disturbances.
The first was impaired absorption of calcium from their diet and the second was excessive obligatory calcium loss in the urine.
This combination of reduced calcium input with excessive calcium output as sufficient to account for their rapid bone loss. The calcium absorption defect was probably located in the gastrointestinal tract itself but was responsive to treatment with calcitriol or i-alpha. The excessive urinary calcium loss might be a manifestation of oestrogen deficiency in the kidneys and was responsive to hormone therapy.
Hip fractures occur in women with excessive cortical bone loss. Professor Nordin suggested that this acceleration could occur quite late in life and might be due to late onset of malabsorption of calcium not necessarily accompanied by excessive urinary loss.
The most likely cause of this late onset of calcium malabsorption was simple vitamin D deficiency due to inadequate exposure to sunlight in elderly individuals, particularly of course those who were housebound.

Sessions Delve into Wide Range of Topics
How widespread is osteoporosis, and who is susceptible to this disease or at high risk? These are important questions because the first step toward prevention is the elimination of risk factors one by one.
The first three sessions called Epidemiology, Risk Factors, Life Style and Peak Bone Mass addressed these problems. The incidence of the most serious complication of osteoporosis, hip feature, various greatly in different parts of the world, higher in Western countries such as the USA and Europe, as was pointed out by Mazzuoli, Kanis, Heyse and Matkovic, than in the Orient, according to Takahashi, Lau and Bose, Mautalen explained the situation in Argentina.
This may be related to life-style and nutrition, according to Dawson Hughes, Anderson, Seeman and Yamamoto. Arnaud disclosed the precious NASA data on osteoporosis in space flight for the first time. Kent discussed the influence of maternity.
Peak bone mass is reached between 30 and 40 years of age followed by a sharp decline especially in females after menopause.
Attempts should therefore be made to achieve as high a peak as possible according to Conrad Johnston, Eisman, Ortolani and Bonjour. DEXA measurement of body composition is quite useful to assess body fat content according to Tsutsumi.
Accurate bone mass measurement along with pertinent biochemical tests would make it possible to detect the disease at an early stage in subjects at high risk for osteoporosis, according to Christiansen. Wasnich and Ross conducted unique studies on Japanese-Americans living in Hawaii to compare genetic and environmental factors in the development of osteoporosis.
Delmas reviewed the use of biochemical data and Melsen histomophometric findings in the diagnosis and classifcationi of osteoporosis. Genant and Morita explained technical problems in bone measurement by DEXA and QCT.
Cytokines represent a new breakthrough to the etiology and pathogenesis of osteoporosis. The rapid postmenopausal bone loss due to increased resorption was explained by the release of IL-I and TNF-a, bone-resorbing cytokines from circulating monocytes by Avioli and Pacifici in response to estrogen withdrawal. Fleisch and Suda emphasized the role of M-CSF in bone resorption.
Manolagas thought IL-6 released in response to estrogen deprivation important for the development of osteoporosis. Ogata and Matsumoto described the role of IGFI on osteoblast proliferation and cell cycle. The role of bone cells in the development of osteoporosis was described by Martin, Mundy and Russel. Imai and Fujita reviewed the relationship between lymphocyte subsets and osteoporosis from a histomorphometric viewpoint.
Bone morphogenic protein purified by Takaoka from osteosarcoma cells is a unique protein capable of producing bone anywhere. Prostaglandin is another local factor essential for bone growth and remodeling as was excellently reviewed by Raisz and discussed by Fukase from the viewpoint of intracellular signal transduction.
For the prevention of osteoporosis, estrogen, calcium and exercise are most important. Rapid bone loss occurring immediately after menopause is best prevented by estrogen replacement as was pointed out by Lindsay and Orimo.
As a matter of fact, "estrogen dogma" has been at the center of osteoporosis research just like "DNA dogma" in biology. An alternative dogma, originally proposed by Nordin, the honorary president of this conference, is "calcium dogma" continually supported by Heaney and Recker. Calcium deficiency is one of the important causes of osteoporosis not only in the immediate postmenopausal period, but also throughout life especially at a higher age. Calcium supplement increases peak bone mass and prevents bone loss. The advent of new readily absorbable calcium preparations widened the scope of calcium supplementation.
According to Fujita, rats live longer on a high calcium diet providing higher bone mass and protecting the development of age-bound anemia, infections, renal and hepatic dysfunction and hyperlipidemia. Vitamin D metabolites extend the effect of calcium as Gallagher, Caniggia and Shiraki asserted.
In addition to the classical augmention of calcium absorption from the gut, vitamin D stimulates cell differentiation, controlling immunity and bone cells, thus increasing bone mass and decreasing fracture rate.
New derivatives such as 24,25(OH)2 vitamin D and 1,25(OH)2 D-26,23 lactone were claimed to stimulate bone formation by Nakamura and Seino. Calcitonin takes the pain away from osteoporotics even at a low intermittent dose popular in Japan, as Morii clearly pointed out.
Fluoride increase bone mass but it has never been used in Japan possibly because its content in water is already high. Ipriflabone was recently added to the armory of physicians to cope with osteoporosis. Parattayrord hormone and disphosphsrates, with digonally different mechanism of action, may represent a candidate to open a new frontier for osteoporosis therapy. Finally, osteoporosis cannot be cured by drugs alone. The importance of exercise reported by Drinkwater and Inoue should not be forgotten.