Bone densitometry update

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Hi All,

The pdf-available below paper may interest for studies of bone densitometry.

Bone densitometry: an update

Science Volume 366, Issue 9503, 2068-2070

Ignac Fogelman and Glen M Blake

Real progress in osteoporosis only came with our ability to diagnose the

condition

before fractures occur, and with development of effective treatments. Bone

densitometry had a crucial role in both. Until the mid-1980s, bone-density

measurements were used mainly for research, and only with the introduction of

dual-energy X-ray absorptiometry (DXA) scanners in 1987 did they enter routine

practice. Further milestones included the finding that bisphosphonate prevents

bone

loss,1 the definition of osteoporosis as a bone-density T score at the spine,

hip,

or forearm of & #8722;2·5 or less,2 and the confirmation that bisphosphonate can

prevent fractures.3 Several trials have now shown the effectiveness of

bisphosphonates,4 selective oestrogen-receptor modulators,5 recombinant

parathyroid

hormone,6 and strontium7 in prevention of fragility fractures.

Today, measurements of bone-mineral density (BMD) are important in the

evaluation of

patients at risk of osteoporosis and in appropriate treatment to prevent

fractures.8

Many centres measure spine and total hip BMD with axial DXA, because of the hip

being the best site for predicting risk of hip fracture,9 the use of the spine

for

monitoring treatment,10 and the consensus that spine and hip BMD results should

be

interpreted with the WHO T-score definition of osteoporosis.8 Devices for

measuring

the peripheral skeleton are available,11 including peripheral DXA (pDXA) for the

forearm, heel, or hand, and quantitative ultrasound for the heel and other

sites.

Because osteoporosis is common and usually managed in primary care, cheap and

convenient methods of evaluating BMD are needed, and peripheral devices might

fulfil

this role. However, the different types of measurement often correlate poorly,

creating a barrier to consensus on the best use of peripheral measurements.12

How do we decide which type of measurement is most effective? Fundamental to the

clinical use of BMD measurements is their ability to predict fracture risk, and

the

best way to evaluate reliability of different techniques is in prospective

studies

of incident fractures.9 These studies use a gradient-of-risk model, in which

findings are expressed as relative risks (increased risk of fracture for 1 SD

decrease from age-adjusted mean BMD). The larger the relative risk, the more

effective a technique is at identifying patients at greatest risk. Until

recently,

however, fracture studies have not had statistical power to properly compare

different types of measurement. The key factor is the number of fractures

recorded

rather than overall study size. To make meaningful comparisons between the

techniques, prospective studies of several hundred patients with fracture are

needed

(figure 1; see webappendix for references). The Study of Osteoporotic Fractures

provides 10 years of follow-up data for hip, spine, heel, and forearm DXA with a

total of 2901 fractures, including 657 hip, 389 vertebral, and 670 wrist

fractures.13 These data have unique statistical power, and confirm that

fractures at

almost every site are associated with low BMD. They show that hip BMD

measurements

are the most effective DXA examination for predicting hip-fracture risk.

In the past few years, another important reason for preference of hip and spine

BMD

measurements has become apparent. Trials of different bisphosphonates have shown

that the patients who respond to treatment are those with a hip or spine T score

of

& #8722;2·5 or less.4 This finding creates a difficulty in use of other

techniques to

select patients for treatment because of a lack of evidence that these

individuals

will respond. The National Osteoporosis Society recommended that peripheral BMD

measurements should be interpreted by triage with device-specific upper and

lower

thresholds defined to give 90% sensitivity and 90% specificity in identifying

patients with osteoporosis at the hip or spine.14 Patients with an equivocal

peripheral T score between the two thresholds should be referred for axial BMD

examination for a decision about suitability for treatment.

Over the past decade, our understanding of osteoporosis has been guided largely

by

the WHO definition.2 Yet, when introduced, this definition was intended for

epidemiological studies and not for diagnosis or treatment guidance. The

rationale

for the clinical use of bone densitometry is the relation between BMD and

fracture

risk, as highlighted in a recent meta-analysis by Olof ell and colleagues.15

By

reducing the concept of fracture risk to one threshold, the WHO definition fails

to

make the best use of the information provided by DXA scanning. A BMD measurement

is

one of several risk factors (including age and history of fracture) that

together

provide the best estimate of risk.16 In the next year or two, a new consensus is

likely to arise, in which information from BMD measurements and clinical risk

factors will be combined to estimate the individual's absolute risk of future

fracture.17

Studies evaluating new treatments for osteoporosis often include follow-up DXA

scans

of several thousand patients. Such numbers are large enough to ensure that even

small BMD changes are highly significant (figure 2; see webappendix for

references).

Nevertheless, the relation between the BMD changes in response to treatment and

the

reduction in fracture risk is controversial, and several studies have concluded

that

much of the fracture prevention by antiresorptive agents is explained by the

reduction in bone resorption rather than the increase in BMD,18 leading to

interest

in methods of measuring bone quality as distinct from bone density. Possible

future

methods include measurements of biochemical markers of bone turnover, and

assessment

of bone microarchitecture.19 Follow-up DXA scans every 1–2 years are also used

in

many osteoporosis clinics to verify response to treatment. Although small

changes in

BMD can be reliably measured in large trials, reliability of follow-up

measurements

in individuals is limited by reproducibility errors.10 The most reliable site is

the

spine, but a BMD change of around 5% is needed to ensure an effect that exceeds

the

least significant change (figure 2).

The UK National Institute for Health and Clinical Excellence has published new

guidelines for the use of bisphosphonates (alendronate, etidronate, and

risedronate), selective oestrogen-receptor modulators (raloxifene), and

parathyroid

hormone (teriparatide) for the treatment of osteoporosis.20 So far these

recommendations only cover secondary prevention of fragility fractures in

postmenopausal women; further guidelines for primary prevention are expected in

the

next year. These guidelines are important for the future use of bone

densitometry in

the UK. They emphasise the part that BMD measurements will continue to play in

management of osteoporosis, prevention of fractures, and cost-effective use of

treatment.

References

1 T Storm, G Thamsborg, T Steiniche, HK Genant and OH Sorensen, Effect of

intermittent cyclical etidronate therapy on bone mass and fracture rate in women

with postmenopausal osteoporosis, N Engl J Med 322 (1990), pp. 1265–1271.

2 WHO Technical Report Series 843, Assessment of fracture risk and its

application

to screening for postmenopausal osteoporosis, World Health Organization, Geneva

(1994).

3 DM Black, SR Cummings and DB Karpf et al., Randomised trial of the effect of

alendronate on risk of fracture in women with existing vertebral fractures,

Lancet

348 (1996), pp. 1535–1541. Abstract | Full Text + Links | PDF (57 K)

4 CH Chesnut, A Skag and C Christiansen et al., Effects of oral ibandronate

administered daily or intermittently on fracture risk in postmenopausal

osteoporosis, J Bone Miner Res 19 (2004), pp. 1241–1249. Abstract-EMBASE |

$Order

Document

5 B Ettinger, DM Black and BH Mitlak et al., Reduction of vertebral fracture

risk in

postmenopausal women with osteoporosis treated with raloxifene: results from a

3-year randomised clinical trial, JAMA 282 (1999), pp. 637–645. Abstract-EMBASE

|

Abstract-MEDLINE | Abstract-Elsevier BIOBASE | $Order Document | Full Text via

CrossRef

6 RM Neer, CD Arnaud and JR Zanchetta et al., Effect of recombinant human

parathyroid hormone (1-34) fragment on spine and non-spine fractures and bone

mineral density in postmenopausal osteoporosis, N Engl J Med 344 (2001), pp.

1434–1441. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE |

$Order

Document | Full Text via CrossRef

7 JY Reginster, E Seeman and MC De Vernejoul et al., Strontium ranelate reduces

the

risk of nonvertebral fractures in postmenopausal women with osteoporosis:

treatment

of peripheral osteoporosis (TROPOS) study, J Clin Endocrinol Metab 90 (2005),

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2816–2822. Abstract-EMBASE | Abstract-Elsevier BIOBASE | $Order Document |

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8 Royal College of Physicians, Osteoporosis: clinical guidelines for prevention

and

treatment, Royal College of Physicians, London (1999).

9 D Marshall, O ell and H Wedel, Meta-analysis of how well measures of bone

mineral density predict occurrence of osteoporotic fractures, BMJ 312 (1996),

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1254–1259. Abstract-EMBASE | Abstract-MEDLINE | $Order Document

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Res 14 (1999), pp. 1952–1962. Abstract-EMBASE | Abstract-MEDLINE | $Order

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11 HK Genant, K Engelke and T Fuerst et al., Noninvasive assessment of bone

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and structure: state of the art, J Bone Miner Res 11 (1996), pp. 707–730.

Abstract-MEDLINE | Abstract-EMBASE | $Order Document

12 Y Lu, HK Genant and J Shepherd et al., Classification of osteoporosis based

on

bone mineral densities, J Bone Miner Res 16 (2001), pp. 901–910. Abstract-EMBASE

|

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13 KL Stone, DG Seeley and L-Y Lui et al., BMD at multiple sites and risk of

fracture of multiple types: long-term results from the Study of Osteoporotic

Fractures, J Bone Miner Res 18 (2003), pp. 1947–1954. Abstract-MEDLINE |

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Document

14 National Osteoporosis Society, Position statement on the use of peripheral

X-ray

absorptiometry in the management of osteoporosis, National Osteoporosis Society,

Bath (2004).

15 O ell, JA Kanis and A Oden et al., Predictive value of BMD for hip and

other

fractures, J Bone Miner Res 20 (2005), pp. 1185–1194. Abstract-MEDLINE |

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16 C De Laet, A Oden, H Johansson, O ell, B Jonsson and JA Kanis, The impact

of

the use of multiple risk factors for fracture on case-finding strategies: a

mathematical approach, Osteoporosis Int 16 (2005), pp. 313–318. Abstract-EMBASE

|

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17 JA Kanis, F Borgstrom and C De Laet et al., Assessment of future risk,

Osteoporosis Int 16 (2005), pp. 581–589. Abstract-MEDLINE | Abstract-EMBASE |

$Order Document | Full Text via CrossRef

18 R Eastell, I Barton, RA Hannon, A Chines, P Garnero and PD Delmas,

Relationship

of early changes in bone resorption to the reduction in fracture risk with

risedronate, J Bone Miner Res 18 (2003), pp. 1051–1056. Abstract-MEDLINE |

$Order

Document

19 RP Heaney, Is the paradigm shifting?, Bone 33 (2003), pp. 457–465. Abstract |

Full Text + Links | PDF (241 K)

20 UK National Institute for Health and Clinical Excellence,

Osteoporosis—secondary

prevention (no 87)http://www.nice.org.uk/page.aspx?o=241341 (June 10, 2005)

(accessed Nov 1, 2005).

Al Pater, PhD; email: old542000@...

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