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3. Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review

Author

Chandran, M; https://orcid.org/0000-0001-9119-8443, Akesson, K E, Javaid, M K, Harvey, N, Blank, R D, Brandi, M L, Chevalley, T, Cinelli, P, Cooper, C, Lems, W, Lyritis, G P, Makras, P, Paccou, J, Pierroz, D D, Sosa, M, Thomas, T, Silverman, S, Fracture Working Group of the Committee of Scientific Advisors o, Chandran, M; https://orcid.org/0000-0001-9119-8443, Akesson, K E, Javaid, M K, Harvey, N, Blank, R D, Brandi, M L, Chevalley, T, Cinelli, P, Cooper, C, Lems, W, Lyritis, G P, Makras, P, Paccou, J, Pierroz, D D, Sosa, M, Thomas, T, Silverman, S, and Fracture Working Group of the Committee of Scientific Advisors o

Abstract

UNLABELLED Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fr

Published
2024

5. Previous fracture and subsequent fracture risk : a meta-analysis to update FRAX

Author

Kanis, J. A., Johansson, H., McCloskey, E. , V, Liu, E., Akesson, K. E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyere, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glueer, C. -c., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W. -p., Koromani, F., Kotowicz, M. A., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellstrom, D., Merlijn, T., Nordström, Anna, Nordström, Peter, O'Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schott, A. -M, Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Vandenput, L., Harvey, N. C., Lorentzon, M., Leslie, W. D., Kanis, J. A., Johansson, H., McCloskey, E. , V, Liu, E., Akesson, K. E., Anderson, F. A., Azagra, R., Bager, C. L., Beaudart, C., Bischoff-Ferrari, H. A., Biver, E., Bruyere, O., Cauley, J. A., Center, J. R., Chapurlat, R., Christiansen, C., Cooper, C., Crandall, C. J., Cummings, S. R., da Silva, J. A. P., Dawson-Hughes, B., Diez-Perez, A., Dufour, A. B., Eisman, J. A., Elders, P. J. M., Ferrari, S., Fujita, Y., Fujiwara, S., Glueer, C. -c., Goldshtein, I., Goltzman, D., Gudnason, V., Hall, J., Hans, D., Hoff, M., Hollick, R. J., Huisman, M., Iki, M., Ish-Shalom, S., Jones, G., Karlsson, M. K., Khosla, S., Kiel, D. P., Koh, W. -p., Koromani, F., Kotowicz, M. A., Kroger, H., Kwok, T., Lamy, O., Langhammer, A., Larijani, B., Lippuner, K., Mellstrom, D., Merlijn, T., Nordström, Anna, Nordström, Peter, O'Neill, T. W., Obermayer-Pietsch, B., Ohlsson, C., Orwoll, E. S., Pasco, J. A., Rivadeneira, F., Schott, A. -M, Shiroma, E. J., Siggeirsdottir, K., Simonsick, E. M., Sornay-Rendu, E., Sund, R., Swart, K. M. A., Szulc, P., Tamaki, J., Torgerson, D. J., van Schoor, N. M., van Staa, T. P., Vila, J., Wareham, N. J., Wright, N. C., Yoshimura, N., Zillikens, M. C., Zwart, M., Vandenput, L., Harvey, N. C., Lorentzon, M., and Leslie, W. D.

Abstract

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX.IntroductionThe aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD).MethodsWe studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted & beta;-coefficients.ResultsA previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination.ConclusionA previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitati

Published
2023
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8. Health systems strengthening to arrest the global disability burden:empirical development of prioritised components for a global strategy for improving musculoskeletal health

Author

Briggs, A. M. (Andrew M.), Huckel Schneider, C. (Carmen), Slater, H. (Helen), Jordan, J. E. (Joanne E), Parambath, S. (Sarika), Young, J. J. (James J.), Sharma, S. (Saurab), Kopansky- Giles, D. (Deborah), Mishrra, S. (Swatee), Akesson, K. E. (Kristina E.), Ali, N. (Nuzhat), Belton, J. (Joletta), Betteridge, N. (Neil), Blyth, F. M. (Fiona M.), Brown, R. (Richard), Debere, D. (Demelash), Dreinhöfer, K. E. (Karsten E.), Finucane, L. (Laura), Foster, H. E. (Helen E.), Gimigliano, F. (Francesca), Haldeman, S. (Scott), Haq, S. A. (Syed A.), Horgan, B. (Ben), Jain, A. (Anil), Joshipura, M. (Manjul), Kalla, A. A. (Asgar A.), Lothe, J. (Jakob), Matsuda, S. (Shuichi), Mobasheri, A. (Ali), Mwaniki, L. (Lillian), Nordin, M. C. (Margareta C.), Pattison, M. (Marilyn), Reis, F. J. (Felipe J. J.), Soriano, E. R. (Enrique R.), Tick, H. (Heather), Waddell, J. (James), Wiek, D. (Dieter), Woolf, A. D. (Anthony D.), March, L. (Lyn), Briggs, A. M. (Andrew M.), Huckel Schneider, C. (Carmen), Slater, H. (Helen), Jordan, J. E. (Joanne E), Parambath, S. (Sarika), Young, J. J. (James J.), Sharma, S. (Saurab), Kopansky- Giles, D. (Deborah), Mishrra, S. (Swatee), Akesson, K. E. (Kristina E.), Ali, N. (Nuzhat), Belton, J. (Joletta), Betteridge, N. (Neil), Blyth, F. M. (Fiona M.), Brown, R. (Richard), Debere, D. (Demelash), Dreinhöfer, K. E. (Karsten E.), Finucane, L. (Laura), Foster, H. E. (Helen E.), Gimigliano, F. (Francesca), Haldeman, S. (Scott), Haq, S. A. (Syed A.), Horgan, B. (Ben), Jain, A. (Anil), Joshipura, M. (Manjul), Kalla, A. A. (Asgar A.), Lothe, J. (Jakob), Matsuda, S. (Shuichi), Mobasheri, A. (Ali), Mwaniki, L. (Lillian), Nordin, M. C. (Margareta C.), Pattison, M. (Marilyn), Reis, F. J. (Felipe J. J.), Soriano, E. R. (Enrique R.), Tick, H. (Heather), Waddell, J. (James), Wiek, D. (Dieter), Woolf, A. D. (Anthony D.), and March, L. (Lyn)

Abstract

Introduction: Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health. Methods: Design: mixed-methods, three-phase design. Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response. Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci. Phase 3: informed by phases 1–2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions. Results: Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action. Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model. Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening. Conclusion: An empirically derived framework, co-designed and strongly supported by multis

Published
2021

9. Risk of imminent fracture following a previous fracture in a Swedish database study

Author

Banefelt, J., Akesson, K. E., Spangeus, A., Ljunggren, Östen, Karlsson, L., Strom, O., Ortsater, G., Libanati, C., Toth, E., Banefelt, J., Akesson, K. E., Spangeus, A., Ljunggren, Östen, Karlsson, L., Strom, O., Ortsater, G., Libanati, C., and Toth, E.

Abstract

The SummaryThis study examined the imminent risk of a future fracture within 1 and 2years following a first fracture in women aged 50years and older and assessed independent factors associated with risk of subsequent fractures. The study highlights the need to intervene rapidly after a fracture to prevent further fractures.IntroductionThis study aims to determine the imminent risk of subsequent fractures within 1 and 2years following a first fracture and to assess independent factors associated with subsequent fractures.MethodsRetrospective, observational cohort study of women aged 50years with a fragility fracture was identified from Swedish national registers. Clinical/demographic characteristics at the time of index fracture and cumulative fracture incidences up to 12 and 24months following index fracture were calculated. Risk factors for subsequent fracture were identified using multivariate regression analysis.ResultsTwo hundred forty-two thousand one hundred eight women (mean [SD] age 74 [12.5] years) were included. The cumulative subsequent fracture incidence at 12months was 7.1% (95% confidence interval [CI], 6.9-7.2) and at 24months was 12.0% (95% CI, 11.8-12.1). The rate of subsequent fractures was highest in the first month (similar to 15 fractures per 1000 patient-years) and remained steady between 4 and 24months (similar to 5 fractures/1000 patient-years). Higher age was an independent risk factor for imminent subsequent fractures (at 24months, sub-distribution hazard ratio [HR], 3.07; p<0.001 for women 80-89years [reference 50-59years]). Index vertebral fracture was a strong independent risk factor for subsequent fracture (sub-distribution HR, 2.72 versus hip fracture; p<0.001 over 12months; HR, 2.23; p<0.001 over 24months).ConclusionsOur findings highlight the need to intervene rapidly after any fragility fracture in postmenopausal women. The occurrence of a fragility fracture provides healthcare systems with a unique opportunity to intervene

Published
2019
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10. Health systems strengthening to arrest the global disability burden:Empirical development of prioritised components for a global strategy for improving musculoskeletal health

Author

Marilyn Pattison, Fiona M. Blyth, Anil Jain, Asgar Ali Kalla, Lillian Mwaniki, Joletta Belton, Dieter Wiek, Sarika Parambath, Neil Betteridge, Syed Atiqul Haq, Manjul Joshipura, Deborah Kopansky-Giles, Jakob Lothe, Richard Brown, Joanne Jordan, Laura Finucane, Francesca Gimigliano, Heather Tick, Ben Horgan, Andrew M. Briggs, Kristina Åkesson, Felipe J J Reis, Demelash Debere, James J. Young, Shuichi Matsuda, Helen E. Foster, Scott Haldeman, Saurab Sharma, Margareta Nordin, Karsten Dreinhöfer, Helen Slater, Carmen Huckel Schneider, Nuzhat Ali, Lyn March, Anthony D. Woolf, Enrique R. Soriano, Swatee Mishrra, James P. Waddell, Ali Mobasheri, Briggs, A. M., Huckel Schneider, C., Slater, H., Jordan, J. E., Parambath, S., Young, J. J., Sharma, S., Kopansky-Giles, D., Mishrra, S., Akesson, K. E., Ali, N., Belton, J., Betteridge, N., Blyth, F. M., Brown, R., Debere, D., Dreinhofer, K. E., Finucane, L., Foster, H. E., Gimigliano, F., Haldeman, S., Haq, S. A., Horgan, B., Jain, A., Joshipura, M., Kalla, A. A., Lothe, J., Matsuda, S., Mobasheri, A., Mwaniki, L., Nordin, M. C., Pattison, M., Reis, F. J. J., Soriano, E. R., Tick, H., Waddell, J., Wiek, D., Woolf, A. D., and March, L.

Subjects
Medicine (General), Economic growth, Guiding Principles, qualitative study, Infectious and parasitic diseases, RC109-216, cross-sectional survey, 03 medical and health sciences, R5-920, 0302 clinical medicine, Blueprint, Political science, health system, 030212 general & internal medicine, Health policy, Original Research, 030203 arthritis & rheumatology, Health Policy, Public Health, Environmental and Occupational Health, Health services research, Global strategy, health policy, health services research, Construct (philosophy), Inclusion (education), health systems, Qualitative research
Abstract

IntroductionDespite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health.MethodsDesign: mixed-methods, three-phase design.Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response.Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci.Phase 3: informed by phases 1–2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions.ResultsPhase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action.Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model.Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening.ConclusionAn empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives.

Published
2021
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11. In community-dwelling women frailty is associated with imminent risk of osteoporotic fractures.

Author

Bartosch P, Malmgren L, Kristensson J, McGuigan FE, and Akesson KE

Subjects
Aged, Bone Density, Female, Frail Elderly, Humans, Independent Living, Frailty epidemiology, Osteoporotic Fractures epidemiology, Osteoporotic Fractures etiology
Abstract

Frailty reflects an accelerated health decline. Frailty is a consequence of fracture and contributes to fracture. Greater frailty was associated with higher fracture risk. Frail women were at immediate risk (within 24 months) of a hip or major fracture. Fracture prevention could be improved by considering frailty status., Introduction: Frailty encompasses the functional decline in multiple systems, particularly the musculoskeletal system. Frailty can be a consequence of and contribute to fracture, leading to a cycle of further fractures and greater frailty. This study investigates this association, specifically time frames for risk, associated fracture types, and how grade of frailty affects risk., Methods: The study is performed in the OPRA cohort of 1044, 75-year-old women. A frailty index was created at baseline and 5 and 10 years. Women were categorized as frail or nonfrail and in quartiles (Q1 least frail; Q4 most frail). Fracture risk was assessed over short (1 and 2 years) and long terms (5 and 10 years). Fracture risk was defined for any fracture, major osteoporotic fractures (MOFs), and hip and vertebral fracture, using models including bone mineral density (BMD) and death as a competing risk., Results: For women aged 75, frailty was associated with higher risk of fracture within 2 years (Hip SHR adj. 3.16 (1.34-7.47)) and MOF (2 years SHR adj. 1.88 (1.12-3.16)). The increased risk continued for up to 5 years (Hip SHR adj. 2.02 (1.07-3.82)); (MOF SHR adj. 1.43 (0.99-2.05)). Grade of frailty was associated with increased 10-year probability of fracture (p = 0.03). Frailty predicted fracture independently of BMD. For women aged 80, frailty was similarly associated with fracture., Conclusion: Frail elderly women are at immediate risk of fracture, regardless of bone density and continue to be at risk over subsequent years compared to identically aged nonfrail women. Incorporating regular frailty assessment into fracture management could improve identification of women at high fracture risk., (© 2021. The Author(s).)

Published
2021
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12. Kidney function and its association to imminent, short- and long-term fracture risk-a longitudinal study in older women.

Author

Malmgren L, McGuigan FE, Christensson A, and Akesson KE

Subjects
Aged, Aged, 80 and over, Female, Glomerular Filtration Rate, Humans, Longitudinal Studies, Risk Factors, Bone Density, Fractures, Bone epidemiology, Kidney physiology, Kidney physiopathology, Osteoporosis epidemiology
Abstract

Reduced kidney function is associated with an increased fracture risk, although the relationship between an age-related decline and fractures needs further investigation. We followed kidney function and fracture risk for 10 years. A mild-moderate decline in kidney function was associated with fracture, but not in advanced age., Introduction: With age, kidney function declines. Though well known that chronic kidney disease is associated with increased fracture risk, the extent to which the typical age-related decline contributes is unclear. In the OPRA cohort, a longitudinal study of older non-selected women, we investigated the association between kidney function and fracture., Methods: Cystatin C-based kidney function estimates were available at age 75 (n = 981) and 80 (n = 685). Women were categorized by kidney function: normal (CKD stages 1 and 2), mild-moderate (3a), poor (3b-5), and imminent, short- and long-term fracture risk investigated. BMD measurements and kidney function for risk prediction were also evaluated; women were categorized by both reduced kidney function (stages 3-5) and osteoporosis status., Results: In the short term, 2-3 years, mild-moderate kidney dysfunction was associated with the highest risk increase: osteoporotic fractures (2 years HR adj 2.21, 95% CI 1.27-3.87) and also up to 5 years (between 75 and 80 years) (HR adj 1.51, 1.04-2.18). Hip fracture risk was similarly increased. This association was not observed from age 80 nor for women with poorest kidney function. Reduced kidney function was associated with higher risk even without osteoporosis (osteoporotic fracture; HR adj 1.66, 1.08-2.54); risk increased by having both osteoporosis and reduced function (HR adj 2.53, 1.52-4.23)., Conclusion: Older women with mild-moderate reduction of kidney function are at increased risk of fractures, but not those with the worst function. Our findings furthermore confirm the value of osteoporosis assessment and it is possible that in this age group, age-related decline of kidney function has limited contribution compared with BMD.

Published
2020
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