Introduction
Site of fracture | Women aged 50 years | Men aged 50 years |
---|---|---|
Hip | 22.9 | 10.7 |
Distal forearm | 20.8 | 4.6 |
Spine (clinical) | 15.1 | 8.3 |
Proximal humerus | 12.9 | 4.9 |
Any of the above | 46.4 | 22.4 |
Men | Women | Total | % | |
---|---|---|---|---|
Acute myocardial infarction | 7,113 | 5,335 | 12,448 | 13.3 |
Cardiovascular accident | 4,411 | 6,069 | 10,480 | 11.2 |
Lung cancer | 1,761 | 1,112 | 2,873 | 3.1 |
Prostate cancer | 2,480 | 0 | 2,480 | 2.6 |
Chronic obstructive airways disease | 944 | 723 | 1,667 | 1.8 |
Diabetes | 744 | 819 | 1,563 | 1.7 |
Breast cancer | 11 | 1,549 | 1,560 | 1.7 |
Hip fracture | 566 | 854 | 1,420 | 1.5 |
Pancreatic cancer | 603 | 736 | 1,339 | 1.4 |
Suicide | 880 | 349 | 1,229 | 1.3 |
Atrial fibrillation | 413 | 687 | 1,091 | 1.2 |
Stomach cancer | 489 | 334 | 823 | 0.9 |
Transport accidents | 422 | 142 | 564 | 0.6 |
Smoke inhalation and fire | 85 | 53 | 138 | 0.2 |
All deaths | 46,840 | 46,788 | 93,628 | 100 |
Bone mineral measurements and diagnosis of osteoporosis
Techniques to measure bone mineral
Site of measurement | Forearm fracture | Hip fracture | Vertebral fracture | All fractures |
---|---|---|---|---|
Distal radius | 1.7 (1.4–2.0) | 1.8 (1.4–2.2) | 1.7 (1.4–2.1) | 1.4 (1.3–1.6) |
Femoral neck | 1.4 (1.4–1.6) | 2.6 (2.0–3.5) | 1.8 (1.1–2.7) | 1.6 (1.4–1.8) |
Lumbar spine | 1.5 (1.3–1.8) | 1.6 (1.2–2.2) | 2.3 (1.9–2.8) | 1.5 (1.4–1.7) |
Diagnostic thresholds
Prevalence of osteoporosis
Men | Women | |||
---|---|---|---|---|
Age range (years) | % of population | Number affected (000) | % of population | Number affected (000) |
50–54 | 2.5 | 7.0 | 6.3 | 17.0 |
55–59 | 3.5 | 7.6 | 9.6 | 21.1 |
60–64 | 5.8 | 11.4 | 14.3 | 30.0 |
65–69 | 7.4 | 14.2 | 20.2 | 43.7 |
70–74 | 7.8 | 14.6 | 27.9 | 63.0 |
75–79 | 10.3 | 13.7 | 37.5 | 68.3 |
80–84 | 16.6 | 14.7 | 47.2 | 67.8 |
50–80 | 6.3 | 83.2 | 21.2 | 310.9 |
Measurement of multiple skeletal sites
Osteopenia
Limitations
General management
Mobility and falls
Number | Risk factor |
---|---|
1. | Impaired mobility, disability |
2. | Impaired gait and balance |
3. | Neuromuscular or musculoskeletal disorders |
4. | Age |
5. | Impaired vision |
6. | Neurological, heart disorders |
7. | History of falls |
8. | Medication |
9. | Cognitive impairment |
Nutrition
Major pharmacological interventions
Effect on vertebral fracture risk | Effect on non-vertebral fracture risk | |||
---|---|---|---|---|
Osteoporosis | Established osteoporosisa
| Osteoporosis | Established osteoporosisa
| |
Alendronate | + | + | NA | + (including hip) |
Risedronate | + | + | NA | + (including hip) |
Ibandronate | NA | + | NA | +b
|
Zoledronic acid | + | + | NA | NA (+)c
|
HRT | + | + | + | + |
Raloxifene | + | + | NA | NA |
Teriparatide and PTH | NA | + | NA | + |
Strontium ranelate | + | + | +(including hip) | + (including hip) |
Selective estrogen-receptor modulators
Bisphosphonates
Peptides of the parathyroid hormone family
Strontium ranelate
Intervention | Study | Entry criteria | Mean age (years) | Number of patients randomised | Fracture incidence (percentage over 3 years)d
| RR (95%CI) | |
---|---|---|---|---|---|---|---|
Placebo | Drug | ||||||
Vertebral fracture (high-risk population) | |||||||
Alendronate 5–10 mg | [51] | Vertebral fractures, BMD ≤ 0.68 g/m2
| 71 | 2,027 | 15.0 | 8.0 | 0.53 (0.41–0.68) |
Risedronate 5 mg | [55] | 2 vertebral fractures or 1 vertebral fracture and T-score ≤−2.0 | 69 | 2,458 | 16.3 | 11.3 | 0.59 (0.43–0.82) |
Risedronate 5 mg | [56] | 2 or more vertebral fractures—no BMD entry criteria | 71 | 1,226 | 29.0 | 18.0 | 0.51 (0.36–0.73) |
Raloxifene 60 mg | [45] | Vertebral fractures—no BMD entry criteria | 66 | 7,705 | 21.2 | 14.7 | 0.70 (0.60–0.90) |
Teriparatide 20 μga
| [65] | Vertebral fractures and FN or LS T-score ≤−1 if less than 2 moderate fractures | 69 | 1,637 | 14.0 | 5.0 | 0.35 (0.22–0.55) |
Ibandronate 2.5 mg | [58] | Vertebral fractures and LS −5<T-score ≤−2.0 | 69 | 2,946 | 9.6 | 4.7 | 0.38 (0.25–0.59) |
Ibandronate 20 mg | [59] | Vertebral fractures and LS –5<T-score ≤−2.0 | 70 | 708 | 9.6 | 4.9 | 0.50 (0.34–0.74) |
Strontium ranelate 2 g | [68] | Vertebral fractures, LS BMD≤0.840 g/m2
| 69 | 1,649 | 32.8 | 20.9 | 0.59 (0.48–0.73) |
Zoledronic acid 5 mg | [63] | FN T score ≤ −2.5, ± vertebral fracture, or T-score ≤ −1.5 and 2+ mild or 1 moderate vertebral fracture | 73 | 7,765 | 10.9 | 3.3 | 0.30 (0.24–0.38) |
Vertebral fracture (low-risk population) | |||||||
Alendronate 5–10 mgb
| [54] | FN T-score ≤−2 | 68 | 4,432 | 3.8 | 2.1 | 0.56 (0.39–0.80) |
Alendronate 5–10 mgb
| [54] | Subgroup of women, T-score <2.5 | NA | 1,631 | 4.0 | 2.0 | 0.50 (0.31–0.82) |
Raloxifene 60 mg | [45] | FN or LS T-score ≤−2.5, ± vertebral fractures | 66 | 7,705 | 4.5 | 2.3 | 0.50 (0.40–0.80) |
Hip fracture | |||||||
Alendronate 5–10 mg | [51] | Vertebral fractures with BMD≤0.68 g/m2
| 71 | 2,027 | 2.2 | 1.1 | 0.49 (0.23–0.99) |
Alendronate 5–10 mgb
| [54] | FN T-score ≤−2c
| 68 | 4,432 | 0.8 | 0.7 | 0.79 (0.43–1.44) |
Alendronate 5–10 mgb
| [54] | FN T-score ≤ − 2.5c (subgroup analysis) | NA | 1,631 | 1.6 | 0.7 | 0.44 (0.18–1.97) |
Risedronate 2.5 and 5 mg | [57] | T-score <−3c or <−2c and ≥1 non-skeletal risk factor for hip fracture (subgroup analysis osteoporotic patients 70–79 years) | 77 | 9,331 | 3.2 | 1.9 | 0.60 (0.40–0.90) |
Raloxifene 60 and 120 mg | [45] | FN or LS T–score ≤−2.5, ± vertebral fractures | 66 | 7,705 | 0.7 | 0.8 | 1.10 (0.60–1.90) |
Strontium ranelate 2 g | [69] | Osteoporosis (T-score < −2.5) with or without prior fracture | 77 | 4,932 | 3.4 | 2.9 | 0.85 (0.61–1.19) |
Strontium ranelate 2 g | [69] | Age ≥ 74 with T-score ≤−2.4c (subgroup analysis) | 80 | 1,977 | 6.4 | 4.3 | 0.64 (0.412–0.997) |
Zoledronic acid 5 mg | [63] | FN T score ≤ −2.5 or less, ± vertebral fracture, or T-score ≤ −1.5 and 2+ mild or 1 moderate vertebral fracture | 73 | 7,765 | 1.4 | 2.5 | 0.59 (0.42–0.83) |
Combination and sequential treatments
Other pharmacological interventions
Calcitonin
Hormone replacement therapy
Etidronate
Vitamin D derivatives
Clodronate
Adherence and monitoring of treatment
Adherence to treatment
Monitoring of treatment with densitometry
Monitoring of treatment with biochemical markers of bone turnover
Assessment of fracture risk
Bone mineral density
Age
Age (years) | Population | T-score = −1 | T-score ≤ −1 | T-score = −2.5 | T-score ≤ −2.5 |
---|---|---|---|---|---|
45 | 0.4 | 0.4 | 0.8 | 1.4 | 2.2 |
50 | 0.6 | 0.5 | 1.1 | 1.7 | 2.9 |
55 | 1.2 | 0.7 | 2.0 | 2.9 | 5.1 |
60 | 2.3 | 1.1 | 3.3 | 4.4 | 7.8 |
65 | 3.9 | 1.5 | 5.0 | 5.9 | 10.9 |
70 | 7.3 | 2.0 | 8.3 | 8.8 | 16.7 |
75 | 11.7 | 2.3 | 11.8 | 11.1 | 21.5 |
80 | 15.5 | 2.5 | 14.6 | 11.5 | 23.8 |
85 | 16.1 | 2.1 | 14.7 | 10.0 | 21.9 |
Other clinical risk factors
Without BMD | With BMD | |||
---|---|---|---|---|
Risk indicator | RR | 95% CI | RR | 95% CI |
Body mass index (20 v 25 kg/m2) | 1.95 | 1.71–2.22 | 1.42 | 1.23–1.65 |
(30 v 25 kg/m2) | 0.83 | 0.69–0.99 | 1.00 | 0.82–1.21 |
Prior fracture after 50 years | 1.85 | 1.58–2.17 | 1.62 | 1.30–2.01 |
Parental history of hip fracture | 2.27 | 1.47–33.49 | 2.28 | 1.48–3.51 |
Current smoking | 1.84 | 1.52–2.22 | 1.60 | 1.27–2.02 |
Ever use of systemic glucocorticoids | 2.31 | 1.67–3.20 | 2.25 | 1.60–3.15 |
Alcohol intake >2 units daily | 1.68 | 1.19–2.36 | 1.70 | 1.20–2.42 |
Rheumatoid arthritis | 1.95 | 1.11–3.42 | 1.73 | 0.94–3.20 |
Biochemical assessment of fracture risk
Case-finding
Risk factor |
---|
Age |
Sex |
Low body mass index |
Previous fragility fracture, particularly of the hip, wrist and spine including morphometric vertebral fracture |
Parental history of hip fracture |
Glucocorticoid treatment (>5 mg prednisolone daily or equivalent for 3 months or more) |
Current smoking |
Alcohol intake 3 or more units daily |
Secondary causes of osteoporosis |
Rheumatoid arthritis |
Untreated hypogonadism in men and women, e.g. premature menopause, bilateral oophorectomy or orchidectomy, anorexia nervosa, chemotherapy for breast cancer, hypopituitarism |
Inflammatory bowel disease, e.g. Crohn’s disease and ulcerative colitis. It should be noted that the risk is in part dependent on the use of glucocorticoids, but an independent risk remains after adjustment for glucocorticoid exposure |
Prolonged immobility, e.g. spinal cord injury, Parkinson’s disease, stroke, muscular dystrophy, ankylosing spondylitis |
Organ transplantation |
Type I diabetes |
Thyroid disorders, e.g. untreated hyperthyroidism, over-treated hypothyroidism |
Chronic obstructive pulmonary disease |
Comparison of case-finding strategies
Age (years) | Number of DXA tests/1000 | Number of high risk women identified/1000* | Number of hip fractures expected* | Number of hip fractures avoided (cost/avoided fracture £000) | |||
---|---|---|---|---|---|---|---|
EUR | WHO | EUR | WHO | EUR | WHO | ||
50 | 450 | 26 | 41 | <1 | 1 | 0.1 (174) | 0.4 (63) |
60 | 450 | 52 | 65 | 2 | 4 | 0.7 (37) | 1.2 (22) |
70 | 500 | 120 | 355 | 16 | 30 | 5.7 (5) | 10.6 (3) |
80 | 550 | 235 | 606 | 51 | 92 | 17.9 (1.8) | 32.0 (1.2) |
Integrating risk factors
Fracture probability
Age (years) | ||||
---|---|---|---|---|
RR | 50 | 60 | 70 | 80 |
(a) Hip fracture | ||||
1 | 0.57 | 2.40 | 7.87 | 18.00 |
2 | 1.14 | 4.75 | 15.1 | 32.0 |
3 | 1.71 | 7.04 | 21.7 | 42.9 |
4 | 2.27 | 9.27 | 27.7 | 51.6 |
(b) Hip, clinical spine, humeral or Colles’ fracture | ||||
1 | 5.8 | 9.6 | 16.1 | 21.5 |
2 | 11.3 | 18.2 | 29.4 | 37.4 |
3 | 16.5 | 26.0 | 40.0 | 49.2 |
4 | 21.4 | 33.1 | 49.5 | 58.1 |
Case finding with fracture probabilities
Category of risk | Index country | Similar countries |
---|---|---|
Very high | Sweden | Denmark |
Iceland | ||
Norway | ||
High | UK | Germany |
Italy | Finland | |
Germany | ||
Greece | ||
Hungary | ||
Netherlands | ||
Portugal | ||
Switzerland | ||
Medium | France | |
Spain | ||
Low | Turkey |
Number of CRFs | BMI (kg/m2) | ||||||
---|---|---|---|---|---|---|---|
15 | 20 | 25 | 30 | 35 | 40 | 45 | |
0 | 7.4 | 6.5 | 6.0 | 5.2 | 4.6 | 4.0 | 3.5 |
1 | 12 (8.4–16) | 10 (7.2–13) | 9.3 (6.5–12) | 8.1 (5.6–11) | 7.0 (4.9–9.2) | 6.1 (4.2–8.0) | 5.3 (3.7–7.0) |
2 | 18 (11–26) | 15 (9.0–24) | 14 (7.9–22) | 12 (6.9–20) | 11 (5.9–17) | 9.2 (5.1–15) | 8.1 (4.4–13) |
3 | 27 (16–40) | 23 (13–36) | 20 (11–34) | 18 (9.5–30) | 16 (8.2–27) | 14 (7.1–24) | 12 (6.1–21) |
4 | 39 (26–53) | 33 (22–47) | 29 (18–44) | 26 (16–39) | 23 (14–35) | 20 (12–31) | 17 (10–27) |
Number of CRFs | BMD T-score (femoral neck) | |||||
---|---|---|---|---|---|---|
−4.0 | −3.0 | −2.0 | −1.0 | 0 | 1.0 | |
0 | 23 | 12 | 7.7 | 5.5 | 4.6 | 4.1 |
1 | 32 (29–37) | 18 (15–21) | 11 (8.2–14) | 8.0 (5.5–11) | 6.8 (4.5–9.5) | 6.0 (3.9–8.4) |
2 | 44 (38–54) | 25 (19–34) | 16 (10–24) | 12 (6.7–18) | 9.8 (5.4–16) | 8.6 (4.6–14) |
3 | 58 (48–68) | 35 (25–49) | 23 (14–36) | 16 (8.7–28) | 14 (6.9–25) | 12 (5.9–22) |
4 | 71 (59–78) | 46 (35–59) | 31 (22–44) | 22 (14–35) | 19 (11–31) | 17 (9.4–28) |
Limitations
Investigation of patients with osteoporosis
Diagnostic work-up
Procedure |
---|
Routine |
History and physical examination |
Blood cell count, sedimentation rate, serum calcium, albumin, creatinine, phosphate, alkaline phosphatase and liver transaminases |
Lateral radiograph of lumbar and thoracic spine |
Bone densitometry (dual energy X-ray absorptiometry) |
Other |
X-ray—vertebral fracture assessment |
Markers of bone turnover, when available |
Differential diagnosis of osteoporosis
Health economics
Types of evaluation
Willingness to pay
Studies of intervention
A reference model
Intervention thresholds
Setting intervention thresholds
Thresholds in the UK
Cost (£000)/QALY gained | |||
---|---|---|---|
Age (years) | T-score = −2.5 | T-score = −2.5 | No BMDa
|
No previous fracture | + Previous fracture | + Previous fracture | |
50 | 38.9 | 14.3 | 28.6 (29.1) |
55 | 31.7 | 16.9 | 27.0 (28.4) |
60 | 29.2 | 15.7 | 23.2 (24.5) |
65 | 16.1 | 8.1 | 11.5 (9.4) |
70 | 10.9 | 4.7 | 6.3 (c.s.) |
75 | 13.3 | 5.4 | 5.2 (c.s.) |
80 | 13.4 | 4.4 | c.s. (c.s.) |
Age (years) | T-score (SD) | |||||||
---|---|---|---|---|---|---|---|---|
0 | −1 | −2 | −3 | 0 | −1 | −2 | −3 | |
Prior fracture | Family history | |||||||
50 | 35.6 | 30.9 | 21.1 | 8.8 | 31.9 | 28.9 | 21.9 | 13.0 |
60 | 35.9 | 30.5 | 20.9 | 8.7 | 30.6 | 27.1 | 20.2 | 12.8 |
70 | 18.7 | 14.2 | 8.5 | 1.0 | 19.0 | 13.7 | 6.8 | c.s. |
80 | 44.7 | 27.9 | 12.7 | c.s. | 27.5 | 6.2 | c.s. | c.s. |
Glucocorticoids | Rheumatoid arthritis | |||||||
50 | 44.1 | 38.8 | 27.0 | 12.2 | 51.5 | 44.4 | 30.5 | 14.3 |
60 | 43.5 | 37.5 | 25.9 | 11.1 | 48.9 | 41.5 | 28.3 | 14.8 |
70 | 21.8 | 16.7 | 9.4 | c.s. | 23.9 | 18.2 | 10.9 | 1.9 |
80 | 46.4 | 27.8 | 8.6 | c.s. | 51.1 | 30.9 | 13.0 | c.s. |
Alcohol >3 units daily | Current smoking | |||||||
50 | 56.1 | 47.8 | 32.0 | 14.1 | 74.5 | 63.1 | 40.6 | 16.9 |
60 | 52.9 | 44.4 | 29.6 | 14.8 | 73.5 | 61.5 | 54.0 | 18.9 |
70 | 26.1 | 19.4 | 11.2 | 1.4 | 37.8 | 28.4 | 16.2 | c.s. |
80 | 53.0 | 31.3 | 12.3 | c.s. | 75.9 | 44.9 | 16.8 | c.s. |
Age (years) | Prior fracture | Secondary OP | FH | Smoking | c.s. | Alcohol |
---|---|---|---|---|---|---|
50 | 28.6 | 46.4 | 32.1 | 64.6 | 43.8 | 52.1 |
55 | 27.1 | 42.2 | 29.9 | 60.1 | 41.0 | 47.7 |
60 | 23.2 | 35.4 | 25.9 | 52.5 | 36.1 | 40.2 |
65 | 11.5 | 17.5 | 13.4 | 27.7 | 18.5 | 20.2 |
70 | 6.3 | 9.5 | 7.5 | 16.6 | 10.0 | 11.6 |
75 | 5.2 | 7.0 | c.s. | 14.8 | 6.3 | 9.8 |
80 | c.s. | c.s. | c.s. | 4.7 | c.s. | 2.2 |
Other treatments
Intervention | T-score = −2.5 SD | No BMD | |
---|---|---|---|
No prior fracture | Prior fracture | Prior fracture | |
Alendronate | 6,225 | 4,727 | 6,294 |
Etidronate | 12,869 | 10,098 | 9,093 |
Ibandronate daily | 20,956 | 14,617 | 14,694 |
Ibandronate intermittent | 31,154 | 21,587 | 21,745 |
Raloxifene | 11,184 | 10,379 | 10,808 |
Raloxifene without breast cancer | 34,011 | 23,544 | 23,755 |
Risedronate | 18,271 | 12,659 | 13,853 |
Strontium ranelate | 25,677 | 18,332 | 19,221 |
Strontium ranelate, post hoc analysis | 18,628 | 13,077 | 13,673 |
Comparison with the National Institute for Health and Clinical Excellence
Comparing osteoporosis with other chronic diseases
Disease | Risk category | |||
---|---|---|---|---|
I | II | III | IV | |
Osteoporosis | BMD T-score = −2.5 SD | BMD T-score = −3.0 SD | BMD T-score = −2.5 SD and prior vertebral fracture | BMD T-score = −3.0 SD and prior vertebral fracture |
Hypertension | SBP = 140 | SBP = 160 | SBP = 140 and diabetes | SBP = 160 and diabetes + smoking |
Hyperlipidaemia | TC 7.25 mmol/l | TC 7.25 mmol/l, HDL 1.3 mmol/l | TC 7.25 mmol/l, HDL 1.3 mmol/l and diabetes | TC 7.25 mmol/l, HDL 1.3 mmol/l, diabetes and smoking |
Age (years) | Risk category | |||
---|---|---|---|---|
I | II | III | IV | |
Osteoporosis | ||||
50 | 80,000 | 53,000 | 29,000 | 21,000 |
60 | 50,000 | 34,000 | 22,000 | 16,000 |
70 | 36,000 | 22,000 | 14,000 | 7,600 |
80 | 21,000 | 9,300 | 5,500 | c.s. |
Hypertension | ||||
50 | 64,000 | 61,000 | 44,000 | 23,000 |
60 | 46,000 | 37,000 | 33,000 | 21,000 |
70 | 33,000 | 32,000 | 29,000 | 24,000 |
80 | 37,000 | 35,000 | 34,000 | 31,000 |
Hyperlipidaemia | ||||
50 | 41,000 | 27,000 | 13,000 | 5,500 |
60 | 40,000 | 27,000 | 19,000 | 16,000 |
70 | 36,000 | 32,000 | 26,000 | 26,000 |
80 | 43,000 | 38,000 | 36,000 | 36,000 |