O Johnell

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (237)910.22 Total impact

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    ABSTRACT: We have in a population-based setting evaluated biochemical markers of bone metabolism in 328 women, aged 40-80 years, and related it to contents of bone mineral measurements and the retrospective and prospective presence of fracture. The participants were recruited from the city population files. Serum samples for analysis of osteocalcin (Oc), procollagen I carboxy-terminal extension peptide (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) were taken, and forearm bone mineral content (BMC) was measured by single photon absorptiometry (SPA). Fracture history was recorded, and the information was verified and supplemented from both radiologic and orthopedic files. Five years later the registration of fractures was repeated. At the initial investigation, Oc was 23% lower in women who had sustained a fracture (n = 37) within 6 years before measurement (6.3 +/- 3.6 microgram/l vs 8.2 +/- 4.2 microgram/l (p = 0.006)), after adjusting for age and BMC difference. PICP and ICTP were not different from values in the women without fracture. However, in women aged 70-80 years with a fracture sustained during the previous 6 years, PICP was lower (128 +/- 32 microgram/l vs 144 +/- 34 microgram/l, p = 0.046). Oc and ICTP were significantly correlated to age and BMC (Oc-age r = 0.36, Oc-BMC r = -0.31, ICTP-age r = 0.44, ICTP-BMC r = -0.24). The correlations of PICP were weaker. Prospectively, logistic regression gave an odds ratio (OR) of 1.8 (p = 0.015) for a low PICP and fracture susceptibility, at a change of 1 SD, independent of age and BMC. In the age bracket 70-80, the odds ratio was 2.4 (p = 0.036). The odds ratio for ICTP, independent of age and BMC, was 1.9 (P = 0.043) for 1 SD decrease and subsequent fracture risk. We concluded that women who had sustained at least one recent fracture had an altered bone turnover with decreased bone formation but an unaltered resorption. Women with retrospectively registered fractures also sustained subsequent fractures. A decrease from the mean of the collagen markers PICP and ICTP was associated with an increased risk for future fracture. Utilizing these biochemical markers of bone metabolism in a female population, PICP and ICTP had a similar influence on the risk of future fracture as forearm BMC (OR = 1.6, p = 0.03).
    No preview · Article · Nov 2009 · Journal of Bone and Mineral Research
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    ABSTRACT: The world population aged more than 50 years will increase in number from 396 million in 1950 to 2129 million in 2025. We are facing an era of elderly, physically increasingly incapacitated populations. Degenerative and other age-dependent disorders, diseases and handicaps will increase in all countries during the next thirty years. Since, in addition, the elderly parts of the populations increase proportionately faster than other age-groups, the increasing economic burden of health expenditure will be carried by relatively smaller parts of populations.
    No preview · Article · Jul 2009 · Scandinavian Journal of Rheumatology
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    ABSTRACT: MEDOS is a case-control study where 9,000 persons were interviewed with an extensive questionnaire, either at time of fracture or in age-matched controls. Both men and women were studied. The MEDOS study has shown that several life-style factors were related with hip fractures, for example a low body mass index is associated with hip fractures and so was low calcium intake. Low physical exercise and immobilization were associated with a higher frequency of hip fractures. The attributable risk has been calculated so one can determine how many hip fractures a specific intervention could reduce, assuming a causal relationship.
    No preview · Article · Jul 2009 · Scandinavian Journal of Rheumatology
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    ABSTRACT: Wrist fracture causes pain and decreased physical, social and emotional function. The International Osteoporosis Foundation has developed a specific questionnaire to assess quality of life in patients with wrist fracture. This questionnaire, including 12 questions, was validated in a multicentre study and compared with an osteoporosis-specific questionnaire (Qualeffo-41) and a generic questionnaire (EQ-5D). The study included 105 patients with a recent wrist fracture and 74 sex- and age-matched control subjects. The questionnaire was administered as soon as possible after the fracture, at 6 weeks, 3 months, 6 months and 1 year after the fracture. Test-retest reproducibility, internal consistency and sensitivity to change were assessed. The results showed adequate repeatability and internal consistency of the International Osteoporosis Foundation (IOF) wrist fracture questionnaire. The discriminatory capacity between patients and control subjects was very high, with significant odds ratios for each question and domain. The IOF-wrist fracture questionnaire domain scores showed significant improvement after 3 and 6 months and some improvement from 6 months up to 1 year. The sensitivity to change was much higher for the IOF-wrist fracture total score than for Qualeffo-41 and EQ-5D. In conclusion, the IOF-wrist fracture questionnaire appears to be a reliable and responsive quality of life questionnaire.
    Full-text · Article · Jul 2009 · Osteoporosis International
  • H Johansson · JA Kanis · A Oden · O Johnell · E McCloskey
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    ABSTRACT: This study examined the effects of the use of clinical risk factors (CRFs) alone, BMD alone or the combination using the FRAX tool for the detection of women at risk of hip fracture. BMD tests alone selected women at higher risk and a greater number of hip fracture cases were identified compared to the use of CRFs alone. The combined use of CRFs and BMD identified fewer women above a threshold risk than the use of BMD alone, but with a higher hip fracture risk and thus had the more favourable positive predictive value (PPV) and number needed to treat (NNT). Algorithms have recently become available for the calculation of hip fracture probability from CRFs with and without information on femoral neck BMD. The aim of this study was to examine the effects of the use of CRFs alone, BMD alone or their combination using the FRAX tool for the detection of women at risk of hip fracture. Data from 10 prospective population based cohorts, in which BMD and CRFs were documented, were used to compute the 10-year probabilities of hip fracture calibrated to the fracture and death hazards of the UK. The effects of the use of BMD tests were examined in simulations where BMD tests were used alone, CRFs alone or their combined use. The base case examined the effects in women at the age of 65 years. The principal outcome measures were the number of women identified above an intervention threshold, the number of hip fracture cases that would be identified, the positive predicted value and the NNT to prevent a hip fracture during a hypothetical treatment with an effectiveness of 35% targeted to those above the threshold fracture risk. We also examined BMD values in women selected for treatment. Sensitivity analysis examined the effect of age and limited use of BMD resources. BMD tests alone selected women at higher risk of hip fracture than the use of CRFs alone (6.1% versus 5.3%). BMD tests alone also identified a greater number of hip fracture cases (219/1,000) compared to the use of CRFs alone (140/1,000). The combined use of CRFs and BMD identified fewer women above a threshold risk than the use of BMD alone (168/1,000 versus 219/1,000, respectively), but with a higher hip fracture risk (PPV, 8.6% versus 6.1%), and consequently a lower number needed to treat (NNT) (33 versus 47). In sensitivity analyses, the PPV and NNT were always better for the combination than either BMD or CRFs alone across all ages studied (50-70 years). The use of FRAX in combination with BMD increases the performance characteristics of fracture risk assessment.
    No preview · Article · Apr 2009 · Osteoporosis International
  • M. Flören · P. Dieppe · O. Johnell · K. Dreinhöfer
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    ABSTRACT: It has been shown that there is international variation in the rates of total hip replacement (THR), partly depending on differences in prevalence and incidence of osteoarthritis but also in part related to the health care systems, the total expenditure on health per capita, the age structure and different indication criteria. According to that literature review, the implantation rates for primary THR varied at the end of the last decade between 50/100,000 and 125/100,000 inhabitants in most European countries and the USA. THR is recognized as cost-effective treatment primarily for osteoarthritis of the hip (70-80%) and fractured neck of the femur (10-20%), and allows for reduction of pain, increased mobility and improved quality of life. Excellent long-term results based on improvements in surgical technique, implant material and design have increased the demand for THR. In addition, joint replacement rates are known to be higher in older age groups and, as the society in the Western World ages, an increase in the number of hip replacements is expected.
    No preview · Article · Jan 2009
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    ABSTRACT: From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2-3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E1) and 17-beta-estradiol (E2) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E2. During the next 3 years, the levels of E2 and E1 showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), delta4-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E1, E2 and T. BMI correlated positively with E1 and E2. The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.
    No preview · Article · Sep 2008 · Maturitas
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    JA Kanis · O Johnell · A Oden · H Johansson · E McCloskey
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    ABSTRACT: A fracture risk assessment tool (FRAX) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m(2)) ranged from 0.2% at the age of 50 years for women without CRF's to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.
    Full-text · Article · May 2008 · Osteoporosis International
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    ABSTRACT: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD. Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score). CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts. The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.
    Full-text · Article · Sep 2007 · Osteoporosis International
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    ABSTRACT: Treatment with alendronate (Fosamax) has been shown to significantly reduce the risk of fragility fractures. Cost-effectiveness of treatment was assessed in nine European countries in a Markov model and was generally found to be cost effective in women with a previous spine fracture. Treatment with alendronate (Fosamax) reduces the risk of osteoporotic fractures at the spine, hip and wrist in women with and without prevalent vertebral fracture. Cost-effectiveness estimates in one country may not be applicable elsewhere due to differences in fracture risks, costs and drug prices. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women with alendronate in nine European countries, comprising Belgium, Denmark, France, Germany, Italy, Norway, Spain, Sweden, and the UK. A Markov model was populated with data for the nine European populations. Effect of treatment was taken from the Fracture Intervention Trial, which recruited women with low BMD alone or with a prior vertebral fracture. The cost per QALY gained of treating postmenopausal women with prior vertebral fractures ranged in the base case from "cost saving" in the Scandinavian countries to 15,000 in Italy. Corresponding estimates for women without prior vertebral fractures ranged from "cost saving" to 40,000. In relation to thresholds generally used, the analysis suggests that alendronate is very cost effective in the treatment of women with previous vertebral fracture, and in women without previous vertebral fracture, cost-effectiveness depends on the country setting, discount rates, and chosen monetary thresholds.
    Full-text · Article · Aug 2007 · Osteoporosis International
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    O Johnell · F Borgstrom · B Jonsson · J.A. Kanis
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    ABSTRACT: Epidemiological observations suggest that sunlight exposure is an important determinant of hip fracture risk. The aim of this ecological study was to examine the relationship between latitude and hip fracture probability. Hip fracture incidence and mortality were obtained from literature searches and 10-year hip fracture probability computed from fracture and death hazards. There was a significant association between latitude and 10-year hip fracture probability. For each 10 degrees change in latitude from the equator (e.g., from Paris to Stockholm), fracture probability increased by 0.3% in men, by 0.8% in women and by 0.6% in men and women combined. There was also a significant association between economic prosperity and hip fracture risk as judged by gross domestic product (GDP)/capita or the use of mobile phones/capita. A US $10,000 higher GDP/capita was associated with a 1.3% increase in hip fracture probability. The association between latitude and hip fracture probability persisted after adjusting for indices of economic prosperity. These findings provide support for an important role of sunlight exposure in the global variation of hip fracture risk. In addition, there is a need to identify the factors related to socioeconomic prosperity that may provide mechanisms for the variation in hip fracture probability worldwide.
    Full-text · Article · Apr 2007 · Osteoporosis International
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    O Johnell · J.A. Kanis
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    ABSTRACT: The aim of this study was to quantify the global burden of osteoporotic fracture worldwide. The incidence of hip fractures was identified by systematic review and the incidence of osteoporotic fractures was imputed from the incidence of hip fractures in different regions of the world. Excess mortality and disability weights used age- and sex-specific data from Sweden to calculate the Disability Adjusted Life Years (DALYs) lost due to osteoporotic fracture. In the year 2000 there were an estimated 9.0 million osteoporotic fractures of which 1.6 million were at the hip, 1.7 million at the forearm and 1.4 million were clinical vertebral fractures. The greatest number of osteoporotic fractures occurred in Europe (34.8%). The total DALYs lost was 5.8 million of which 51% were accounted for by fractures that occurred in Europe and the Americas. World-wide, osteoporotic fractures accounted for 0.83% of the global burden of non-communicable disease and was 1.75% of the global burden in Europe. In Europe, osteoporotic fractures accounted for more DALYs lost than common cancers with the exception of lung cancer. For chronic musculo-skeletal disorders the DALYs lost in Europe due to osteoporosis (2.0 million) were less than for osteoarthrosis (3.1 million) but greater than for rheumatoid arthritis (1.0 million). We conclude that osteoporotic fractures are a significant cause of morbidity and mortality, particularly in the developed countries.
    Preview · Article · Jan 2007 · Osteoporosis International
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    ABSTRACT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
    No preview · Article · Dec 2006 · Journal of Clinical Endocrinology & Metabolism
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    F Borgström · O Johnell · JA Kanis · B Jönsson · C Rehnberg
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    ABSTRACT: Intervention thresholds (ITs), the 10-year hip fracture risk at which treatment can be considered to be cost-effective, have previously been estimated for Sweden and the UK. The aim of this study was to provide a Markov cohort model platform for a multinational estimation of thresholds at which intervention becomes cost-effective and to investigate and determine the main factors behind differences in these thresholds between countries. Intervention thresholds were estimated for Australia, Germany, Japan, Sweden, Spain, the UK and USA using a societal perspective. The model was populated with as much relevant country-specific data as possible. Intervention was assumed to be given for 5 years and to decrease the risk of all osteoporotic fractures by 35%. The societal willingness to pay (WTP) for a quality-adjusted life-year (QALY) gained was set to the gross domestic product (GDP) per capita multiplied by two. In the base case analysis, the 10-year hip fracture probability at which intervention became cost-effective varied across ages and countries. For women starting therapy at an age of 70 years, the IT varied from a hip fracture probability of 5.6% in Japan to 14.7% in Spain. The main factors explaining differences in the IT between countries were the WTP for a QALY gained, fracture-related costs and intervention costs. The ITs presented in this paper are appropriate for use in treatment guidelines that consider health economic aspects, and they can be used in combination with fracture risk prediction algorithms to improve the selection of patients who are suitable for osteoporotic intervention.
    Full-text · Article · Nov 2006 · Osteoporosis International
  • Article: PD02.03

    No preview · Article · Nov 2006 · Urology

  • No preview · Article · Nov 2006 · Revue du Rhumatisme

  • No preview · Article · Nov 2006
  • O. Johnell · L. Lidgren · P. Wagner · D. Mellstrom

    No preview · Conference Paper · Sep 2006
  • O Johnell

    No preview · Article · May 2006 · Annales d Endocrinologie

  • No preview · Article · May 2006 · Revue de Chirurgie Orthopédique et Réparatrice de l Appareil Moteur

Publication Stats

23k Citations
910.22 Total Impact Points


  • 2009
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 1977-2008
    • Lund University
      • • Department of Orthopaedics
      • • Department of Surgery
      • • Department of Radiation Physics
      • • Department of Orthopedic Surgery
      Lund, Skåne, Sweden
  • 1996-2007
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
    • Stockholm School of Economics
      • Department of Economics
      Tukholma, Stockholm, Sweden
    • University of Amsterdam
      • Department of Endocrinology
      Amsterdamo, North Holland, Netherlands
  • 1992-2007
    • Malmö University
      Malmö, Skåne, Sweden
  • 2006
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
    • Södersjukhuset
      Tukholma, Stockholm, Sweden
  • 1999-2005
    • The University of Sheffield
      • Medical School
      Sheffield, England, United Kingdom
  • 2004
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1997-2003
    • University of Cambridge
      • • Department of Medicine
      • • Cambridge Institute of Public Health
      Cambridge, ENG, United Kingdom
  • 1998
    • Mayo Clinic - Rochester
      • Department of Health Science Research
      Rochester, Minnesota, United States
  • 1994-1997
    • The University of Manchester
      • School of Nursing, Midwifery and Social Work
      Manchester, England, United Kingdom