Introduction
Background
Fracture risk assessment and case finding
Recommendations
Risk variable | Adjustment to FRAX* | Access |
---|---|---|
Medium and high dose exposure to oral glucocorticoids | Medium doses (2.5–7.5 mg daily) are the assumed minimum requirement for FRAX calculation, and the unadjusted FRAX value is used. For high doses (> 7.5 mg daily), MOF probabilities are upward revised by about 15% and hip fracture probabilities by 20% ¥ | Automatic adjustment available on FRAX website |
Concurrent data on lumbar spine (LS) BMD | Increase/decrease MOF probability by 10% for each rounded T-score difference between LS and FN* | Leslie et al. 2011 |
Trabecular bone score (TBS) | Increase MOF probability by 30% for each standard deviation (SD) decrease in TBS | |
Hip axis length (HAL) | Increase hip fracture probability by 30% for each SD increase in HAL | |
Falls history | Increase MOF and hip fracture probability by 30% for a history of recurrent falls (≥ 2 falls in the last year) | |
Country of birth | Use FRAX model for country of birth since individuals retain the risk characteristics of their country of origin | |
Type II diabetes mellitus | Enter ‘yes’ in the rheumatoid arthritis input to FRAX | |
Recent MOF | Marked uplift to fracture probabilities (see Sect. 4 h) |
Measurement of bone mineral density
Assessment of clinical risk factors
Fracture risk assessment tools
Investigation of osteoporosis and fragility fractures
Routine | Other procedures, if indicated |
---|---|
Clinical history Physical examination including measurement of height and assessment of thoracic kyphosis Full blood cell count Erythrocyte sedimentation rate or C-reactive protein Serum calcium, albumin, creatinine, phosphatea, alkaline phosphatasea, and liver transaminases Serum 25-hydroxyvitamin D Thyroid function tests | Serum electrophoresis, serum immunoglobulins, and serum-free light chain assay Plasma parathyroid hormone (PTH)b Serum testosterone, sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone 24-h urinary free cortisol/overnight dexamethasone suppression test Serum prolactin Serum magnesium if hypocalcemic Tissue transglutaminase antibodies, ± endomysial antibodies (coeliac disease screen) Urinary calcium excretion Markers of bone turnover (e.g., CTX, P1NP)c Lateral radiographs of lumbar and thoracic spine or DXA based lateral vertebral imaging Bone densitometry (DXA) if indicated by FRAX assessment and/or required for BMD monitoring Isotope bone scan |
Vertebral fracture assessment
Screening and case finding
Thoracic kyphosis |
Height loss (> 4 cm) |
Falls and Frailty |
Inflammatory disease: e.g., ankylosing spondylitis, other inflammatory arthritides, connective tissue diseases, systemic lupus erythematosus |
Endocrine disease: e.g., type I and II diabetes mellitus a, hyperparathyroidism, hyperthyroidism, hypogonadism, Cushing’s disease/syndrome |
Haematological disorders/malignancy e.g., multiple myeloma, thalassaemia |
Muscle disease: e.g., myositis, myopathies and dystrophies, sarcopenia |
Lung disease: e.g., asthma, cystic fibrosis, chronic obstructive pulmonary disease |
HIV |
Neurological/ psychiatric disease e.g., Parkinson’s disease and associated syndromes, multiple sclerosis, epilepsy, stroke, depression, dementia |
Nutritional deficiencies: calcium, vitamin D [note that vitamin D deficiency may contribute to fracture risk through undermineralisation of bone (osteomalacia) rather than osteoporosis] |
Bariatric surgery and other conditions associated with intestinal malabsorption |
Medications, e.g.: |
Some immunosuppressants (calmodulin/calcineurine phosphatase inhibitors) |
(Excess) thyroid hormone treatment (levothyroxine and/or liothyronine). Patients with thyroid cancer with suppressed TSH are at particular risk |
Drugs affecting gonadal hormone production (aromatase inhibitors, androgen deprivation therapy, medroxyprogesterone acetate, gonadotrophin hormone-releasing agonists, gonadotrophin hormone receptor antagonists) |
Some diabetes drugs (e.g., thiazolidinediones) |
Some antiepileptics (e.g., phenytoin and carbamazepine) |
Intervention thresholds and strategy
Recommendations
-
⚬ The presence of single but important clinical risk factors, such as the following:
-
A recent vertebral fracture (within the last 2 years)
-
≥ 2 vertebral fractures (whenever they have occurred)
-
BMD T-score ≤ − 3.5
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Treatment with high dose glucocorticoids (≥ 7.5 mg/day of prednisolone or equivalent over 3 months) (refer urgently given rapid loss in bone post-initiation of glucocorticoids; if any delay is anticipated, start an oral bisphosphonate in the meantime)
-
⚬ The presence of multiple clinical risk factors, particularly with a recent fragility fracture indicating a high imminent risk of re-fracture
-
⚬ Or other indicators of very high fracture risk.
FRAX assessment thresholds for 10-year probability of fracture
Indications for specialist referral in those at very high-fracture risk
Age (years) | LAT | IT | UAT | VHRT |
---|---|---|---|---|
Major osteoporotic fracture | ||||
50 | 3.4 | 7.3 | 8.8 | 11.7 |
55 | 4.5 | 9.5 | 11.4 | 15.2 |
60 | 6.0 | 12.2 | 14.6 | 19.4 |
65 | 8.6 | 16.5 | 19.8 | 26.4 |
70 | 11.1 | 20.3 | 24.4 | 32.5 |
Hip fracture | ||||
50 | 0.23 | 0.91 | 1.1 | 1.5 |
55 | 0.43 | 1.5 | 1.7 | 2.3 |
60 | 0.80 | 2.3 | 2.8 | 3.7 |
65 | 1.4 | 3.5 | 4.2 | 5.6 |
70 | 2.6 | 5.4 | 6.5 | 8.6 |
FRAX—practical considerations
Non-pharmacological management of osteoporosis
Recommendations
Dietary modification
Calcium and vitamin D
Exercise to improve or maintain bone density
Falls interventions
Lifestyle measures
Pharmacological treatment options
Recommendations
Antiresorptive drug treatment
Anabolic drug treatment
Other treatments
Overview of treatment options
Intervention | Vertebral fracture | Non-vertebral fracture | Hip fracture | Evidence of superiority or inferiority for vertebral fracture prevention in postmenopausal women with very high fracture risk | Licenced for use in men |
---|---|---|---|---|---|
Romosozumab | Ib | IIb | IIb | Superior to alendronate (Ib) | No |
Teriparatide | Ia | Ia | Ia | Superior to risedronate (Ib) | Yes |
Alendronate | Ia | Ia | Ia | Inferior to romosozumab (Ib) | Yes |
Ibandronate | Ib | Ib | NAE | NAE | No |
Risedronate | Ia | Ia | Ia | Inferior to teriparatide (Ib) | Yes |
Zoledronate | Ia | Ia | Ia | NAE | Yes |
Calcitriol | IIa | NAE | NAE | NAE | Yes |
Denosumab | Ia | Ia | Ia | NAE | Yes |
HRT | Ia | Ia | Ia | NAE | No |
Raloxifene | Ia | NAE | NAE | NAE | No |
Strontium Ranelate | Ia | Ia | IIb | NAE | Yes |
Primary and secondary care drug initiation
Secondary care drug initiation.
Treatment sequence
Specific drug options
Anti-resorptive drugs: bisphosphonates
Contraindications and special precautions for the use of bisphosphonates
Anti-resorptive drugs: denosumab
Anti-resorptive drugs: hormone-replacement therapy
Anti-resorptive drugs: calcitriol
Anti-resorptive drugs: raloxifene
Other drugs: strontium ranelate
Anabolic drugs: teriparatide (recombinant human parathyroid hormone [PTH] 1–34)
Anabolic drugs: romosozumab
Drug treatment for patients with very high fracture risk
Duration and monitoring of bisphosphonate treatment
Recommendations
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Age ≥ 70 years at the time that the bisphosphonate is started
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Who have a previous history of a hip or vertebral fracture(s)
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Treated with oral glucocorticoids ≥ 7.5 mg prednisolone/day or equivalent
-
Who experience one or more fragility fractures during the first 5 years of treatment (if treatment is not changed).
-
Age ≥ 70 years at the time that the bisphosphonate is started
-
Who have a previous history of a hip or vertebral fracture(s)
-
Treated with oral glucocorticoids ≥ 7.5 mg prednisolone/day or equivalent
-
Who experience one or more fragility fractures during the first 3 years of treatment (if treatment is not changed).
Reassessment of fracture risk in individuals on osteoporosis drug treatment
Recommendations
Rare adverse effects of long-term bisphosphonate and denosumab treatment
Recommendations
Glucocorticoid-induced osteoporosis
Recommendations
Bone protective therapy | Spine BMD | Hip BMD | Vertebral fracture | Non-vertebral fracture | Evidence of superiority for spine and/or hip BMD |
---|---|---|---|---|---|
Alendronate | Ib | Ia | Ia | Ia | Inferior to teriparatide (Ib) |
Risedronate | Ib | Ia | Ia | NAE | Inferior to zoledronate (Ia) |
Zoledronate | Ib | Ib | Ia | NAE | Superior to risedronate (Ib) |
Denosumab | Ib | Ia | Ia | NAE | Superior to bisphosphonates (IIa) |
Teriparatide | Ib | Ib | Ia | Ia | Superior to alendronate (Ib) |
Dose | Prednisolone equivalent dose (mg/day) | Average adjustment to hip fracture probability | Average adjustment to major osteoporotic fracture (MOF) probability |
---|---|---|---|
Low | < 2.5 | − 35% | − 20% |
Medium | 2.5–7.5 | None | None |
High | ≥ 7.5 | + 20% | + 15% |
Men receiving androgen-deprivation therapy
Recommendations
Women receiving aromatase inhibitor therapy
Recommendations
osteoporosis and fracture, with bisphosphonates or denosumab (strong recommendation).
Management of symptomatic osteoporotic vertebral fractures
Recommendations
Models of care for fracture prevention
Recommendations
FLS models of care
FLS patient identification
Providing patient information and adherence support
Recommendations for training
Recommendations
Examples of appropriate training
Recommendations for commissioners of healthcare
Recommendations
Review criteria for audit and quality improvement
Quality standards for osteoporosis
Primary care
Fracture liaison services
DXA reporting
Summary of main recommendations
Concerning the assessment of fracture risk in postmenopausal women, and men aged ≥ 50
Regarding drug treatment to prevent fractures in postmenopausal women, and men aged ≥ 50
When selecting drug treatments to prevent fractures in postmenopausal women, and men aged ≥ 50
When postmenopausal women, and men aged ≥ 50, have started drug treatment
When postmenopausal women, and men aged ≥ 50, are treated with oral glucocorticoids
When advising on lifestyle and dietary measures
Regarding fracture prevention services
When a postmenopausal woman, or a man aged ≥ 50, has a symptomatic osteoporotic vertebral fracture
Appendix 1
List of stakeholders
External reviewers
Appendix 2. Grading of evidence
Levels of evidence for studies of intervention
Levels of evidence for the validity of candidate risk factors
Grading of recommendations
Appendix 3. AMSTAR2 grading of systematic reviews and meta-analyses
Topic | Reference | Type of study | AMSTAR2 grading | Reference |
---|---|---|---|---|
Fracture risk assessment and case finding | Bai et al. 2020 | MA | Low | [60] |
Gausden et al. 2017 | SR | Medium | [100] | |
Johannesdottir et al. 2018 | SR | Low | [42] | |
Kanis et al. 2016 | SR | Medium | [79] | |
Marshall et al. 1996 | MA | Critically Low | [29] | |
Merlijn et al. 2019 | SR & MA | Critically Low | [107] | |
Mortensen et al. 2020 | SR & MA | Medium | [66] | |
Singh-Ospina et al. 2017 | SR & MA | Low | [73] | |
Vilaca et al. 2020 | SR & MA | Low | [59] | |
Zhang et al. 2020 | SR & MA | Low | [109] | |
Intervention thresholds and management strategy | Kanis et al. 2016 | SR | Medium | [79] |
Non-pharmacological management of osteoporosis | Babatunde et al. 2020 | SR & MA | Medium | [160] |
El-Khoury et al. 2013 | SR & MA | Medium | [166] | |
Darling et al. 2019 | SR & MA | Medium | [144] | |
Fabiani et al. 2019 | SR & MA | Medium | [141] | |
Gillespie et al. 2012 | SR & MA | High | [170] | |
Groenendijk et al. 2019 | SR & MA | Medium | [143] | |
Iguacel et al. 2018 | SR & MA | High | [146] | |
Howe et al. 2011 | SR & MA | High | [158] | |
Jepsen et al. 2017 | SR & MA | Medium | [171] | |
Kahwati et al. 2018 | SR & MA | Medium | [155] | |
Kelley et al. 2000 | SR & MA | Medium | [161] | |
Kemmler et al. 2020 | SR & MA | Low | [159] | |
Kunutsor et al. 2018 | SR & MA | Medium | [163] | |
Min et al. 2017 | SR & MA | Low | [174] | |
Shen et al. 2015 | SR & MA | Medium | [173] | |
Sherrington et al. 2017 | SR & MA | Low | [169] | |
Sherrington et al. 2019 | SR & MA | High | [167] | |
Yao et al. 2019 | SR & MA | Medium | [151] | |
Zhao et al. 2019 | SR & MA | Low | [168] | |
Pharmacological treatment options | Diez-Perez et al. 2019 | SR & MA | Medium | [228] |
Gartlehner et al. 2017 | SR & MA | Medium | [215] | |
Nayak et al. 2017 | SR & MA | Low | [313] | |
Poon et al. 2018 | SR & MA | Low | [273] | |
Simpson et al. 2020 | SR & MA | Medium | [229] | |
Zeng et al. 2019 | SR & MA | Medium | [314] | |
Strategies for management of osteoporosis and fracture risk | Deng et al. 2020 | SR & MA | Low | [266] |
Dennison et al. 2019 | SR | Medium | [204] | |
Gedmintas et al. 2013 | SR & MA | Medium | [259] | |
Khan et al. 2015 | SR | Medium | [252] | |
Miyashita et al. 2020 | SR & MA | Low | [278] | |
Nayak et al. 2019 | SR & MA | High | [241] | |
Tsourdi et al. 2020 | SR | Medium | [202] | |
Wang et al. 2018 | SR & MA | Critically Low | [315] | |
Yanbeiy et al. 2019 | SR & MA | Low | [316] | |
Management of symptomatic osteoporotic vertebral fractures | Al-Sari et al. 2016 | SR & MA | Low | [15] |
British Geriatric Society 2013 | SR | Medium | [281] | |
Buchbinder et al. 2018 | SR & MA | High | [289] | |
Ebeling et al. 2019 | SR & MA | Critically Low | [286] | |
Gibbs et al. 2019 | SR | Medium | [285] | |
Hofler et al. 2020 | SR | Low | [288] | |
Knopp-Sihota et al. 2012 | SR & MA | Medium | [282] | |
Svensson et al. 2017 | SR | Low | [287] | |
Models of care for fracture prevention | Ganda et al. 2013 | SR & MA | Critically Low | [297] |
Ganda et al. 2019 | SR & MA | Low | [298] | |
Martin et al. 2020 | SR & MA | Medium | [306] | |
Paskins et al. 2020 | SR | Medium | [303] | |
Wu et al. 2018 | SR | Critically Low | [292] | |
Wu et al. 2018 | SR & MA | Low | [299] |