Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK continued

Clinical risk factors

• At present there is no universally accepted policy for population screening in the UK to identify individuals with osteoporosis or those at high risk of fracture

• Patients are identified opportunistically using a case-finding strategy on the finding of a previous fragility fracture or the presence of significant clinical risk factors (CRFs)

• Some of these risk factors act independently of BMD to increase fracture risk (see below) whereas others increase fracture risk through their association with low BMD (e.g. some of the secondary causes of osteoporosis listed below)

• Clinical risk factors used for the assessment of fracture probability:
• age
• sex
• low body mass index (≤19kg/m²)
• previous fragility fracture, particularly of the hip, wrist, and spine including morphometric vertebral fracture
• parental history of hip fracture
• current oral glucocorticoid treatment (any dose for 3 months or more)
• current smoking
• alcohol intake of 3 or more units daily
• secondary causes of osteoporosis, including:
• rheumatoid arthritis
• untreated hypogonadism in men and women
• prolonged immobility
• organ transplantation
• type I diabetes
• hyperthyroidism
• gastrointestinal disease
• chronic liver disease
• chronic obstructive pulmonary disease
• falls (not presently accommodated in the FRAX^® algorithm)

• In general, smoking and alcohol are weak risk factors; secondary causes of osteoporosis are moderate risk factors; prior fracture or a parental history of hip fracture are strong risk factors. Glucocorticoid therapy maybe a moderate or strong risk factor, depending on the dose and duration of therapy. In patients on higher doses (e.g. >15 mg/day of prednisolone or equivalent for more than 3 months) fracture probability maybe underestimated using FRAX^®

• Note that the only secondary cause of osteoporosis that contributes to fracture risk when should be used with BMD is rheumatoid arthritis

The FRAX^® tool

• The FRAX^® algorithm can integrate the number of CRFs for fracture risk with or without information on BMD

• The online FRAX^® tool (www.shef.ac.uk/FRAX) computes the 10-year probability of hip fracture or a major osteoporotic fracture (clinical spine, hip, forearm, or humerus).Probabilities can be computed for several countries, including the UK

Case finding

• Fracture risk should be assessed in postmenopausal women and in men aged 50 years or more with the risk factors outlined where assessment would influence management

• Women with a prior fragility fracture can be considered for treatment without the need for further risk assessment although BMD measurement may be appropriate, particularly in younger postmenopausal women

• In the presence of other CRFs, the 10-year probability of a major osteoporotic fracture (clinical spine, hip, forearm, or humerus) should be determined using FRAX^®. This value can then be transferred on to the graphs shown in Figure 1

• Assessment and treatment threshold:
• men and women with probabilities below the lower assessment threshold can be reassured
• those with probabilities above the lower assessment threshold but below the upper assessment threshold can be considered for testing with BMD using DXA and their fracture probability reassessed
• men and women with probabilities above the intervention threshold should be considered for treatment

• In men and women who require a BMD test, fracture probabilities should be recomputed with FRAX^®. Treatment can be considered in those in whom fracture probabilities lie above the intervention threshold

• There are a number of other indications for bone densitometry, including monitoring of treatment, determination of the extent of bone loss, and assessment of suitability for certain treatments

• The intervention threshold at each age is set at a risk equivalent to that associated with a prior fracture and, therefore, rises with age. The proportion of women in the UK potentially eligible for treatment rises from 20% to 40% with age

• Probabilities of a major osteoporotic fracture (as well as hip fracture probabilities) can be plotted at the NOGG web site (www.shef.ac.uk/NOGG) available through FRAX^®

Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK continued

Figure 1. Assessment and treatment thresholds without (left) or with (right) a BMD test to compute fracture probability for men and women

Figure taken from: Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A and the National Osteoporosis Guideline Group (2008) Case finding for the management of osteoporosis with FRAX^®–Assessment and intervention thresholds for the UK. Osteoporos Int 19: 1395–1408.). © The International Osteoporosis Foundation and National Osteoporosis Foundation, reprinted with permission.

Treatment of osteoporosis

• General management includes:
• assessment of the risk of falls and their prevention
• maintenance of mobility
• correction of nutritional deficiencies; in particular (with recommended daily intake):
• calcium (1000 mg)
• vitamin D (800 IU)
• protein (1 g/kg body weight)

• Major pharmacological interventions:
• bisphosphonates
• denosumab
• strontium ranelate
• raloxifene
• parathyroid hormone peptides

• All these interventions have been shown to reduce the risk of vertebral fracture when given with calcium and vitamin D supplements. Some have been shown to also reduce the risk of non-vertebral fractures, in some cases specifically at the hip (see table)

• The low cost of generic alendronate, which has a broad spectrum of anti-fracture efficacy, makes this the first-line treatment in the majority of cases

• In individuals who are intolerant of alendronate or in whom it is contraindicated, other bisphosphonates, denosumab, strontium ranelate or raloxifene may provide appropriate treatment options. The high cost of parathyroid hormone peptides restricts their use to those at very high risk, particularly for vertebral fractures

• Alendronate, risedronate, teriparatide, and zoledronate are also approved for treatment of men at high risk of fracture

• Alendronate is approved for the prevention and treatment of glucocorticoid-induced osteoporosis

• Risedronate and etidronate are approved for the prevention and treatment of glucocorticoid-induced osteoporosis in postmenopausal women

• Zoledronate is approved for the treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in post-menopausal women and men at increased risk of fracture

• Teriparatide is approved for treatment of glucocorticoid-induced osteoporosis in men and women at increased risk of fracture

• Other approved pharmacological interventions for postmenopausal women include calcitonin, calcitriol, etidronate, and hormone replacement therapy

• Monitoring of treatment commonly uses repeated estimations of BMD and markers of bone formation and/or bone resorption

The intervention thresholds provided in the NOGG guidance provide a starting point for making treatment decisions, but do not replace clinical judgement in the management of individual patients in clinical practice

Guidelines for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK continued

Effect of major pharmacological interventions on fracture risk when given with calium and vitamin D in postmenopausal women with osteoporosis

Intervention	Vertebral fracture	Non-vertebral fracture	Hip fracture
Alendronate	A	A	A
Ibandronate	A	A1	nae
Risedronate	A	A	A
Zoledronate	A	A	A
Denosumab	A	A	A
Raloxifene	A	nae	nae
Strontium ranelate	A	A	A1
Teriparatide	A	A	nae
PTH (1-84)	A	nae	nae

A=Recommendation based on meta-analysis of randomised controlled trials (RCT) or at least one RCT; nae=not adequately evaluated; ¹in subsets of patients (post-hoc analysis); PTH recombinant human parathyroid hormone

Table taken from: Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A and the National Osteoporosis Guideline Group (2008) Case finding for the management of osteoporosis with FRAX^®– Assessment and intervention thresholds for the UK. Osteoporos Int 19: 1395–1408). © The International Osteoporosis Foundation and National Osteoporosis Foundation, reprinted with permission.

full guidelines available from…
http://www.shef.ac.uk/NOGG
http://www.link.com/

National Osteoporosis Guideline Group. Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK. October 2008, updated July 2010