Osteoporosis cost-effectiveness of therapy

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{{Osteoporosi[s}} Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Cost-Effectiveness of Therapy

  • In 1984, femoral fracture, the main complication of osteoporosis costed about ₤48 million per year, in England and Wales.[1]
  • In 1987, osteoporosis was the most prevalent musculoskeletal disorder in North America. 15-20 million adults were affected, involves 1.3 million fractures; led to annual cost of $3.8 billion for treatment. The estimated 267000 femoral neck fractures, in 1980, caused costs of $1.3 billion just for acute management. The average hospital stays were 21 days.[2]

Osteoporosis - Incidence and burden

  • Regarding that osteoporosis is the main cause of 8.9 million fractures in a year, whole over the world, it can be concluded that osteoporosis leads to one fracture in every 3 seconds.[3]
  • The estimated women population under the burden of osteoporosis influence is about 200 million, worldwide; two third of them 90, two fifth of them 80, one fifth of them 70, and one tenth of them 60 years old.
  • The total share of Europe, USA, and Japan in osteoporosis is about 75 million people.[4]
  • Women have rate of fracture in forearm, humerus, hip, and spine as 80%, 75%, 70%, and 58%, respectively. However, women encounter the fractures 1.6 times more than men, total of 61% of osteoporotic fractures.[3]
  • It is estimated than in 2050, the rate of hip fracture will increase 310% and 240% in male and females, respectively, in contrast with 1990.[5]
  • When the lifetime risks of fractures in hip, forearm, and vertebrae become clinically interpreted, it will equal to 40%, that is the same as cardiovascular events.[6]
  • In Europe the social and economical effects of osteoporosis is greater than that resulted from cancers (except lung cancer), and also higher than rheumatoid arthritis, asthma, and cardiac disease due to hypertension.[3]
  • Women of more than 45 years old spend more days in hospital due to osteoporosis and its complications than any other disease, such as diabetes, myocardial infarction, and breast cancer.[7]
  • It is assumed that large percentage (almost 80%) of individuals with high risk of fracture and already history of at least one osteoporotic fracture, are neither identified nor treated.[8]
  • International osteoporosis foundation (IOF) study in 11 countries, showed that lack of oteoporosis suitable diagnosis and treatment were because of some factors, including denial of personal risk by postmenopausal women, lack of dialogue about osteoporosis with their doctor, and restricted access to diagnosis and treatment before the first fracture.[9]

Europe

  • In most of the European countries, bone mineral density (BMD) measurements are not so utilized; it is assumed to be due densitometers limited availability, limited technicians in charge of performing scans, low attitude and insight in using the test, and limited or nonexistent reimbursement.[10]
  • WHO estimation of the osteoporosis population in Europe is 22 million females and 5.5 million males in 2010 (total of 27.5 million); which is going to rise about 23% until 2025 (total of 33.9 million). New fractures in the EU during 2010 was estimated at 3.5 million, including approximately 620,000 hip fractures, 520,000 vertebral fractures, 560,000 forearm fractures and 1,800,000 other fractures. The number of fractures in a year assumed to grow from 3.5 million in 2010 to 4.5 million in 2025, suggesting a 28% increase. 43,000 people have died in 2010 because of osteoporosis complications. It is assumed that osteoporotic fractures are the main reason of 26,300 life-year lost in Europe, in 2010.[11]
  • In Europe the whole cost of medical therapies for osteoporosis in 2010 was €37 billion, in which 66% was for acute fractures management, 29% was for long-term fracture outcome management, and 5% was for medical prevention. On the other hand, holistic burden of osteoporosis in Europe assumed to be loss of 1,180,000 life years (quality adjusted (QALY)), most of them because of prior osteoporotic fractures. Regarding that one QALY is equal value of 2xGDP, it is assumed that the total burden of osteoporosis become €60.4 billion, in 2010. Surprisingly, the QALY number will raise from 1.2 million in 2010 to about 1.4 million years in 2025, with 20% increase.[11]
The economic burden of osteoporosis, in 2010 and 2025[12]
Country Year New osteoporotic fractures People over 50 with osteoporosis Economic burden each year Economic burden by 2025 2025 increase percentage
Germany 2010 725,000 5,020,000 € 9 billion (€ 9,008 million) € 11.2 billion (€11,261 million) 25%
UK 2010 536,000 3,210,000 £ 3,496 (€ 5,408) million £ 5,465 (€ 6,723) million 24%
France 2010 377,000 3,480,000 € 4,853 million € 6,111 million 26%
Spain 2010 204,000 2,450,000 € 2,842 million € 3.68 billion 30%
Sweden 2010 107,000 520,000 € 1,486 million € 1.8 billion (€ 1,828 million) 23%
Denmark 2010 66,000 280,000 € 1,055 million €1.3 billion (€ 1,344 million) 27%
Greece 2010 86,000 640,000 € 680 million € 814 million 20%
Belgium 2010 80,000 600,000 € 606 million € 733 million 21%
Romania 2010 94,000 590,000 € 577 million € 151 million 17%
Czech Republic 2010 72,000 530,000 € 273 million € 352 million 29%
Slovenia 2010 16,000 590,000 € 56 million € 77 million 37%

Denmark

From 1987-1997, in a 10-year period, the rate of osteoporosis increased by 56%; among which 41% was in women and 104% was in men, more than 50 years old.[13]

Finland

Hip fracture rate increased by 70% from 1992 to 2002, in a 10-year period.[14]

Georgia

It is assumed that only one patient with hip fracture out of four is seeking hospital care.[15]

Germany

A study of fracture rate showed that 45% of men and 31% of women between 25 to 74 years old experience fracture; while 42% of men and 40% of women between 65 to 74 years old encounter fractures.[16]

Greece

Hip fracture rate was increased by 7.6% from 1977 until 1992, in a five year period.[17]

Kazakhstan

Due to some various factors, more than half of the people with hip fracture are not hospitalized. Whereas more than 70% are not admitted for hip surgery.[18]

Romania

The whole prevalence of postmenopausal osteoporosis is 11.5%. It is assumed that in Romanian women more than 55 years old, one out of three people involved in osteoporosis or osteopenia.[18]

Russia

14 million people (about 10%) are involved in osteoporosis, while 20 million suffer from osteopenia; however, Russia has 34 million high fracture risk people. It is assumed that in some cities 45-52% of patients with a severe osteoporotic fracture have not suitable hospitalization or surgery until 1 year. Among those patients with hip fracture who could survive, only about 10% would have previous daily activity level.[18]

Slovenia

General hip fracture rate has been increased by 40% from 1998 to 2005, a seven year period.[18]

Spain

The increase rate of new hip fracture case was 54% from 1998 to 2002, a 14-year period. However, the women (64%) were more increased than men (19%).[19]

The fracture was leading to demise of 13% of patients after 3 months, and 38% of them after 24 months. Furthermore, patients suffered from vertebral fracture would experienced loosing functionality (45%) or disability (50%).

Sweden

23% of women and 11% of men over 50 years of age are probable to involved in osteoporotic fracture. Also, 15% of women and 8% of men have the risk of vertebral fractures. Any other oteoporotic fractures during lifetime are 46% in women and 22% in men.[20] The total death rate resulting from hip fractures is the same as breast cancer deaths.[21]

Switzerland

It is predicted that with maintaining the current conditions of osteoporotic prevention and treatment, in a 20 years period from 2000, the osteoporotic fracture rates of hip, vertebrae, and wrist grow by 33%, 27%, and 19%, respectively.[22]

It is assumed that annual economic burden of osteoporosis is commonly greater than myocardial infarction, cerebrovascular strokes, and also breast cancer; slightly less than chronic obstructive pulmonary disease. Taking only women, the burden become more than all of the diseases.[23]

Ukraine

7 million womens (28% of all women) are involved in bone mass loss and in risk of osteoporosis. Most of the Ukrainians experiencing vitamin D insufficiency or deficiency.[18]

UK

Half of women and one-fifth of men would have fracture when pass 50 years of age.[24]

North America

Canada

  • : Osteoporosis affects approximately 1.4 million Canadians, mainly postmenopausal women and the elderly (142). Osteoporosis affects 1 in 4 women and more than 1 in 8 men over the age of 50 years, with 1 in 4 men and women having evidence of a vertebral fracture (142,167).
  • Canada: Almost 30,000 hip fractures occur each year (142). By the year 2030, the number of hip fractures is expected to quadruple (165,166).
  • USA: Osteoporosis and low bone mass are currently estimated to be a major public health threat for almost 44 million U.S. women and men aged 50 and older. (241).
  • USA: The 44 million people with either osteoporosis or low bone mass represent 55 percent of the people aged 50 and older in the United States (241).
  • USA: By the year 2010, it is estimated that more than 52 million women and men in this same age category will be affected and, if current trends continue, the figure will climb to more than 61 million by 2020 (241).
  • USA: In 2002, it is estimated that more than 10 million people already have osteoporosis. Approximately eighty percent of these people are women. This figure will rise to almost 12 million individuals by 2010 and to approximately 14 million by 2020 if additional efforts are not made to stem this disease, which may be largely prevented with lifestyle considerations and treatment when appropriate (241).

Latin America

  • From 1990 to projections in 2050 the number of hip fractures for women and men aged 50-64 in Latin America will increase by 400%. For age groups older than 65 the increase will be a staggering 700% (24).
  • Latin Americans will suffer an estimated 655,648 hip fractures in 2050, at an estimated direct cost of $13 billion (143). The mortality rates in the year following a hip fracture are 23-30% and are higher in men compared to women (235,236).
  • The prevalence of vertebral osteopenia in women 50 years and older has been reported at 45.5-49.7% and vertebral osteoporosis at at 12.1-17.6%; while the prevalence of femoral neck osteopenia has been reported at 46-57.2% and femoral neck osteoporosis at 7.9-22% (235).
  • In a study of five Latin American countries (Argentina, Brazil, Colombia, Mexico and Puerto Rico), the prevalence of vertebral fractures in women over 50 years of age was about 15%, with 7% occuring within the 50-60 years old age group and increasing to 28% for those greater than 80 years old (186).
  • Argentina: The prevalence in women over 50 years old is 50% for osteopenia and 25% for osteoporosis (237). It is projected that by 2050, 5.24 million and 2.62 million women will have osteopenia and osteoporosis, respectively (238).
  • Argentina: 34,000 hip fractures occur every year in the population aged 50 years and older, with an average of 90 fractures/day. By 2050, there will be >63,000 hip fractures in women and >13,000 in men (239). The prevalence of vertebral fractures in these women is 16.2% (186). Hospitalization costs of hip and vertebral fractures exceed 190 million USD per year (239).
  • Brazil: 10 million people, approximately one person in every 17, has osteoporosis (144). The lifetime prevalence of fractures has been found to be 37.5% among men and 21% among women with proportions among white, mixed and black subjects at about 29%, 31% and 22%, respectively (187).
  • Brazil: It is estimated that just 1 in 3 patients with hip fractures are diagnosed as having osteoporosis and of those, only 1 in 5 receive any kind of treatment (192).
  • Brazil: The economic burden of osteoporosis hip fractures to private health plan companies in Brazil is estimated in the region of $6 million (191).
  • Chile: In 1985, a large clinical trial of women older than 50 indicated that 46% had osteopenia and 22% had osteoporosis (145).
  • Mexico: 1 out of every 4 people has osteopenia or osteoporosis (146) and the lifetime probability of having a hip fracture at 50 years of age is 8.5% for women and about 4% for men (188). For 2006, the estimated cost of healthcare for hip fracture was $97 million (189).
  • Venezuela: The lifetime probability of having a hip fracture at 50 years of age is 5.5% for women and 1.5% for men, and for any osteoporotic fracture is 13.6% for women and 3.5% for men (236).
  • Venezuela: In 1995 there were 9.6 hip fractures per day. In 2030 it is estimated that there will be 67 hip fractures per day. Of the people that suffer a hip fracture, 17% die in the first 4 months after the fracture. Clinical trials indicated that only the 10% of the population older than 70 years have normal peak bone mass (147).

Middle East and Africa

  • Despite ample sunshine, the Middle East and Africa register the highest rates of rickets worldwide. Low levels of vitamin D are prevalent throughout the region (247).
  • Mortality rates post-hip fracture may be higher in this region than those reported from western populations. While such rates vary between 25-30% in western populations, they are 2-3 fold higher in populations from the Middle East and Africa region (248).
  • There are extremely limited numbers of DXA machines available in this region.  In Morocco, there are only 0.6 DXA machines per 1 million people (247).
  • Egypt: Calculations show that 53.9% of postmenopausal women have osteopenia while 28.4% have osteoporosis (249).  21.9% of males aged 20-89 have osteoporosis (247).
  • Iran: It hasaccounted for 0.85% of the global burden of hip fracture and 12.4% of the burden of hip fracture in the Middle East (215).
  • Iran: There were 50,000 hip fractures in 2010 and 62,000 are projected for 2020 (215).
  • Jordan: Currently, it is estimated that there are 1008 hip fractures per year in Jordan, however, based on the First Jordanian Hip Fracture Survey (2008) it is predicted that this number will quadruple by 2050 (247).
  • Lebanon: Hip fractures occur at a younger age in Lebanon compared to Western populations, and 60% of patients with hip fractures have osteopenia rather than osteoporosis (250).
  • Qatar: A 2009 study of 458 children revealed that 68.8% were vitamin D deficient. The deficiency was most pronounced in the age group 11-16 years (251).
  • Saudi Arabia: With a population of 1,461,401 persons aged 50 years or more, 8768 would suffer femoral fractures yearly at a cost of $1.14 billion (219).
  • Syria: It is estimated that there are about 15,000 vertebral fractures each year of which only 20% are treated by a doctor (247).
  • Turkey: More than 24,000 hip fractures occurred annually in men and women aged 50 years and over in 2010, and 36,000 are projected for 2020 (252).

Asia

  • It is projected that more than about 50% of all osteoporotic hip fractures will occur in Asia by the year 2050 (7,24)
  • Osteoporosis is greatly underdiagnosed and undertreated in Asia, even in the most high risk patients who have already fractured. The problem is particularly acute in rural areas. In the most populous countries like China and India, the majority of the population lives in rural areas (60% in China), where hip fractures are often treated conservatively at home instead of by surgical treatment in hospitals (221).
  • DXA technology is relatively expensive and is not widely available in most developing Asian countries, especially in rural areas. For example, in 2008 Indonesia had a total of only 34 DXA machines, half of them in Jakarta, for a population of ca. 237 million (0.001 per 10,000 population). Like in many Asian countries, this falls far below the recommended number for Europe, of 0.11 per 10,000 (221).
  • Nearly all Asian countries fall far below the FAO/WHO recommendations for calcium intake of between 1000 and 1300 mg/day. The median dietary calcium intake for the adult Asian population is approximately 450 mg/day, with a potential detrimental impact on bone health in the region (221).
  • Studies carried out across different countries in South and South East Asia showed, with few exceptions, widespread prevalence of vitaminosis D (vitamin D deficiency/insufficiency), in both sexes and all age groups of the population (222).
  • China: Osteoporosis affects almost 70 million Chinese over the age of 50 and causes some 687,000 hip fractures in China each year (223). From 1988 to 1992, the incidence of hip fractures in Beijing increased by 34% in women and 33% in men (151). There is a higher incidence of hip fractures in men than in women in China (151,152,153).
  • China: The overall prevalence of osteoporosis in mainland China might be approximately 7% among adults, 10-20% in urban areas, 22.5% among men aged 50 years or more, and 50.1% among women aged 50 years or more (231).
  • China: The average direct cost of a hip fracture in 2007 was 3603 USD and statistics from different cities indicate that the cost of hip fracture has been increasing at a rate of 6% per year. In 2006 China spent ca. 1.5 billion USD treating hip fracture. It is estimated that this will rise to 12.5 billion USD in 2020 and by 2050 to more than 264.7 billion USD (224,225,226,227,228,229).
  • China: Osteoporosis prevention and awareness is largely restricted to urban areas of China and DXA machines are only available in the urban centers. In 2008 there were only 450 DXA machines in China for a population of ca. 1.3 billion (223).
  • China: The average length of hospital stay (19-24 nights) for a hip fracture exceeds that for treating breast cancer, ovarian cancer, prostate cancer or heart disease (223).
  • Hong Kong, China: Epidemiological studies showed that hip fracture incidence had increased by 300% from the 1960s to 1990s, and has stabilized from 2001-2006. The reasons are not clear, but may possibly be due to a number of factors including improved availability of medical intervention, increases in BMI, use of HRT, and improved falls prevention strategies (155,221).
  • Hong Kong, China: Despite the stabilization of hip fracture rates, fractures remain a major burden on health services and society. The acute hospital care cost of hip fractures amounted to 1% of the total annual hospital budget, or 17 million USD for a population of 6 million (154).
  • Hong Kong, China: The prevalence of vertebral fractures is estimated at 30% in women and 17% in men between the ages of 70-79 years of age. These rates are comparable to those in American Caucasians (148,149,156).
  • Chinese Taipei: The prevalence of osteoporosis in 1996-2001 among those ages 50 years and older was 1.6% in men and 11.4% in women (232). A study showed a high incidence rate of hip fractures, close to those of Western countries, and substantially higher than the rates in Beijing (3-5 times) and Hong Kong (1-2 times), except after age 85 (230). During 1996-2002, the incidence of hip fractures in the 65 years and older population increased by 30%, with rates greater in males (36%) than females (22%) (233).
  • India: Expert groups peg the number of osteoporosis patients at approximately 26 million (2003 figures) with the numbers projected to increase to 36 million by 2013 (157).
  • India: In a study among Indian women aged 30-60 years from low income groups, BMD at all the skeletal sites were much lower than values reported from developed countries, with a high prevalence of osteopenia (52%) and osteoporosis (29%) thought to be due to inadequate nutrition (193).
  • Japan: The prevalence of osteporosis in the Japanese female population aged 50-79 years has been estimated to be about 35% at the spine and 9.5% at the hip (150).
  • Japan: New hip fractures increased 1.7-fold during 1987-1997 (158).
  • Japan: The total number of hip fractures is forecast to be 153,000 per year in 2010 and 238,000 in 2030 (202).
  • Korea: The occurrence of hip fractures increased about 4-fold over 10 years (1991-2001) (159).
  • Korea: The number of hip fractures after 75 years of age was 4.3 per 1000 in women and 2.97 per thousand in men (160).
  • Pakistan: Osteoporosis seems to be a significant problem due to major nutritional issues as well as limited and underutilised diagnostic facilities (221).
  • Singapore: The incidences of hip fracture in 1998 have gone up 5 times in women and 1.5 times in men compared to those observed in the 1960s (161). During 1991-1998, the incidence of hip fracture increased by 0.7% annually in men and by 1.2% annually in women (234).

Oceania

  • Australia: 2.2 million Australians are affected by osteoporosis (163). About 11% of men and 27% of women aged 60 years or more are osteoporotic, and 42% of men and 51% of women are osteopenic (162).
  • Australia: The lifetime risk of osteoporotic fracture after 50 years of age: 42% in women, 27% in men (163).
  • Australia: There are 20,000 hip fractures per year in Australia (increasing by 40% each decade) (163).
  • Australia: Total costs relating to osteoporosis are $7.4 billion per year of which $1.9 billion are direct costs (163).
  • New Zealand: There were an estimated 84,000 osteoporotic fractures in 2007, with 60% of these occurring in women. Hip fractures were estimated to account for 5% of all fractures (138).
  • New Zealand: The total cost of osteoporosis is estimated to be over $1.15 billion per year (138).
  • New Zealand: It is estimated that both the number of osteoporotic fractures and the cost of healthcare associated with osteoporosis will increase by over 30% between 2007-2020 (138).

References

  1. ↑ Smith R (1984). "Osteoporosis--a problem of bone formation?". Postgrad Med J. 60 (704): 383–5. PMC 2417886. PMID 6379627.
  2. ↑ Martin AD, Houston CS (1987). "Osteoporosis, calcium and physical activity". CMAJ. 136 (6): 587–93. PMC 1491904. PMID 3545420.
  3. ↑ 3.0 3.1 3.2 Johnell O, Kanis JA (2006). "An estimate of the worldwide prevalence and disability associated with osteoporotic fractures". Osteoporos Int. 17 (12): 1726–33. doi:10.1007/s00198-006-0172-4. PMID 16983459.
  4. ↑ "Who are candidates for prevention and treatment for osteoporosis?". Osteoporos Int. 7 (1): 1–6. 1997. PMID 9102057.
  5. ↑ Gullberg, B.; Johnell, O.; Kanis, J.A. (1997). "World-wide Projections for Hip Fracture". Osteoporosis International. 7 (5): 407–413. doi:10.1007/PL00004148. ISSN 0937-941X.
  6. ↑ Kanis JA (2002). "Diagnosis of osteoporosis and assessment of fracture risk". Lancet. 359 (9321): 1929–36. doi:10.1016/S0140-6736(02)08761-5. PMID 12057569.
  7. ↑ Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D (1997). "Guidelines for diagnosis and management of osteoporosis. The European Foundation for Osteoporosis and Bone Disease". Osteoporos Int. 7 (4): 390–406. PMID 9373575.
  8. ↑ Nguyen TV, Center JR, Eisman JA (2004). "Osteoporosis: underrated, underdiagnosed and undertreated". Med. J. Aust. 180 (5 Suppl): S18–22. PMID 14984358.
  9. ↑ "How Fragile is Her Future | International Osteoporosis Foundation".
  10. ↑ "Osteoporosis in the European Community: A Call to Action | International Osteoporosis Foundation".
  11. ↑ 11.0 11.1 Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J; et al. (2013). "Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA)". Arch Osteoporos. 8: 136. doi:10.1007/s11657-013-0136-1. PMC 3880487. PMID 24113837.
  12. ↑ Svedbom A, Hernlund E, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA (2013). "Osteoporosis in the European Union: a compendium of country-specific reports". Arch Osteoporos. 8: 137. doi:10.1007/s11657-013-0137-0. PMC 3880492. PMID 24113838.
  13. ↑ Giversen IM (2006). "Time trends of age-adjusted incidence rates of first hip fractures: a register-based study among older people in Viborg County, Denmark, 1987-1997". Osteoporos Int. 17 (4): 552–64. doi:10.1007/s00198-005-0012-y. PMID 16408148.
  14. ↑ Lönnroos E, Kautiainen H, Karppi P, Huusko T, Hartikainen S, Kiviranta I, Sulkava R (2006). "Increased incidence of hip fractures. A population based-study in Finland". Bone. 39 (3): 623–7. doi:10.1016/j.bone.2006.03.001. PMID 16603427.
  15. ↑ "www.iofbonehealth.org" (PDF).
  16. ↑ Meisinger C, Wildner M, Stieber J, Heier M, Sangha O, Döring A (2002). "[Epidemiology of limb fractures]". Orthopade (in German). 31 (1): 92–9. PMID 11963475.
  17. ↑ Paspati I, Galanos A, Lyritis GP (1998). "Hip fracture epidemiology in Greece during 1977-1992". Calcif. Tissue Int. 62 (6): 542–7. PMID 9576984.
  18. ↑ 18.0 18.1 18.2 18.3 18.4 "Eastern European & Central Asian Audit | International Osteoporosis Foundation".
  19. ↑ Hernández JL, Olmos JM, Alonso MA, González-Fernández CR, Martínez J, Pajarón M, Llorca J, González-Macías J (2006). "Trend in hip fracture epidemiology over a 14-year period in a Spanish population". Osteoporos Int. 17 (3): 464–70. doi:10.1007/s00198-005-0008-7. PMID 16283063.
  20. ↑ Kanis JA, Johnell O, Oden A, Sembo I, Redlund-Johnell I, Dawson A, De Laet C, Jonsson B (2000). "Long-term risk of osteoporotic fracture in Malmö". Osteoporos Int. 11 (8): 669–74. PMID 11095169.
  21. ↑ Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B, Oglesby AK (2003). "The components of excess mortality after hip fracture". Bone. 32 (5): 468–73. PMID 12753862.
  22. ↑ Schwenkglenks M, Lippuner K, Häuselmann HJ, Szucs TD (2005). "A model of osteoporosis impact in Switzerland 2000-2020". Osteoporos Int. 16 (6): 659–71. doi:10.1007/s00198-004-1743-x. PMID 15517190.
  23. ↑ Lippuner K, von Overbeck J, Perrelet R, Bosshard H, Jaeger P (1997). "Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland". Osteoporos Int. 7 (5): 414–25. PMID 9425498.
  24. ↑ van Staa TP, Dennison EM, Leufkens HG, Cooper C (2001). "Epidemiology of fractures in England and Wales". Bone. 29 (6): 517–22. PMID 11728921.

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