Postgraduate Training Course in Reproductive Health/Chronic Disease

The measurement of bone mass

René Rizzoli, M.D.
Division of Bone Diseases
WHO Collaborating Center for the Prevention of Osteoporosis
Department of Internal Medicine
University Hospital
CH 1211 Geneva 14 (Switzerland)

See also :

• Osteoporosis, genetics and hormones

• Osteoporosis in the frail elderly: A special case?

• A comprehensive review of treatments for postmenopausal osteoporosis

Introduction

Osteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture risk. The diagnosis of the disease relies thus on the quantitative assessement of bone mineral mass/density, which represents so far one of the best determinants of bone strength. Thus, the diagnosis of osteoporosis is not based on the demonstration of fracture, which constitutes a complication, or the clinical expression of the disease, but on parameters capable of reliably predicting the risk of fracture.

Dual-energy absorptiometry

There are many techniques available to assess bone mass. They measure bone mineral content, or areal bone mineral density, which is the amount of bone mineral divided by the bone scanned area. Dual x-ray absorptiometry (DXA) techniques are now validated for this measurement not only at two skeletal sites particularly at risk of osteoporotic fracture, such as lumbar spine and proximal femur, but also at the peripheral skeleton such as the forearm. For the diagnosis of osteoporosis, hip and/or spine are mainly to be considered. BMD accounts for more than two thirds of the variance of bone strength as determined in vitro on isolated skeletal pieces, such as the vertebral body. There is an inverse relationship between incidence of osteoporotic fracture and DXA-provided BMD values. Long term longitudinal studies have demonstrated that a decrease of 1 SD in lumbar spine BMD (in anteroposterior view) is associated with a 2.6 to 5.8 fold increase in fracture risk, comparable with a 10-17-year increase in years after menopause. These techniques provide  information on the amount of bone at a specific skeletal sites. Areal bone mineral density (BMD) integrates the size of the bone and its thickness, as well as the true volumetric density. The introduction of an X-ray, instead of an isotope source and then of multiarray detectors of the photon fluxes have considerably lowered the time of scanning and improved the precision of the measurement. These most useful clinical measurements now constitute necessary non-invasive tools for the diagnosis and follow-up of osteoporosis.

The strength of vertebral body assessed in vitro appears to be better correlated with BMD values obtained in lateral than in anteroposterior view. Furthermore, gender differences in vertebral body BMD are detectable in lateral view. Lumbar spine BMD measurements in lateral view could also offer the advantage over conventional anteroposterior projection of avoiding osteophytes and posterior elements osteoarthritis. However, the interest in measurement of lateral spine has decreased for various reasons including the superposition of ribs and/or pelvis, reducing the number of vertebrae analysable. This lower number of vertebrae measurable compromises the precision of the measurements. Furthermore, rotation of the spine and possible thicker soft tissue to be crossed by the photon beam make it more difficult to clearly define the limits of the vertebral body, adding imprecision to BMD determination. For a longitudinal follow up, lateral BMD, at least with present technology does not appear to be of clinical advantage, since the precision error of the measurement is more than double the annual bone loss after menopause. Thus, it does not seem to be superior in diagnostic sensitivity, except possibly for corticosteroid-induced bone loss.

Femoral neck BMD appears to be a better predictor of fracture of the proximal femur. This is based on long-term prospective longitudinal studies with fracture as outcome. Since this measurement seems to be influenced by osteoarthritis to a much lower extent than the spine, it would be the most suitable one for the diagnosis of osteoporosis in elderly. Above the age of 65, spine can barely be considered for diagnosis purpose. DXA measurements are also providing information on other local determinant of fracture risk. Indeed, in a prospective study, hip axis length, but not neck-shaft angle or neck width was associated independently of BMD with a higher fracture risk (relative risk of 1.8 for hip axis length and 2.1 for BMD). Estimation of fracture risk is not improved by determining volumetric density, with ROC analysis indicating a trend in favor of BMD measurements. This demonstrates that predictive power can be improved by including macroarchitecture data. However, proximal femur measurements are influenced by a variety of factors likely to impair accuracy and decrease precision of the measurement. The size of the region of interest as well as its location along the hip axis, the degree of leg rotation can affect proximal femur BMD measurement. Indeed, subcapital instead of basicervical location of the region of interest is associated with higher absolute BMD values and with a worse precision. The potential for error in terms of both accuracy and precision for dual x-ray absorptiometry measurements of lumbar spine and proximal femur emphasizes the need for strictly controlled conditions of measurements.

A WHO panel has proposed the limit of -2.5 standard deviations below the mean values recorded in young healthy individuals of the same gender as the diagnostic criterion for osteoporosis (T-Score ; T-Score = [measured BMD – Young Adult BMD] / Young Adult SD). The fracture rate in this reference population is very low. This approach is very similar to the measurement of blood pressure for the diagnosis of hypertension. This constitutes a diagnosis threshold, which should not be automatically translated into a therapeutic threshold. Indeed, other factors such as age, concommittant risk factors, bone turnover or treatment cost/benefits, should be included into the treatment decision. The prevalence of subjects with bone mass values below this limit increases with age, reaching approximately 40 % at the age of 80. Indeed, this prevalence correponds to the life-time risk of any skeletal fracture in a 50-year old woman. However, it should be reminded that there is no BMD threshold value for the risk of osteoporotic fracture, but the relationship is characterized by a continuous increasing gradient of risk with the decrease of BMD. Z-Score compares a patient’s value with the mean BMD of age-, gender- and ethnic origin-matched healthy subjets (Z-score = [measured BMD – Age-matched mean BMD] / Age-Matched SD). It provides an estimate of fracture risk as compared with healthy age- and gender-matched subjects.

Whole body bone, fat and lean masses can also be measured using DXA. These variables provide interesting and useful information in the frame of research protocols, but they are not of any help in the routine diagnosis of osteoporosis at the present time.

Computerized tomography

Quantitative computerized tomography (QCT) can be applied to both the axial and appendicular skeleton. It provides information on tridimentional volumetric density, and can distinguish between the cortical and cancellous bone envelops, and evaluate shape and architecture. A simultaneously scanned bone phantom is used to calibrate the density measurements. Since cancellous bone is more responsive to many therapeutical interventions, this technique could be of theoretical interest to monitor treatment at the level of the vertebral body. However, a lower reproductibilty at least for the central assessement of the axial skeleton, the radiation exposure, or the cost of the instruments, represent real disadvantages. For measurements at the peripheral skeleton level, instruments are under development capable of an in vivo spatial resolution lower than 200 µm. These systems can measure the forearm or the distal tibia volumetric density with extremely high precision. 

Quantitative ultrasound

Quantitative ultrasound (QUS) measurement techniques, based on the evaluation of ultrasound velocity and attenuation, have been introduced for the assessment of bone status in osteoporosis. The calcaneus, because of its large volume of trabecular bone, and readily accessible, but also the phalangeae are chosen for transmission measurements. The physical measurements are an measure of the attenuation of ultrasounds through the bone (broadband ultrasonic attenuation, BUA, expressed in decibels per megahertz) and the speed of sound (SOS). Both BUA and SOS are lower in patients with osteoporosis. Data are accumulating in favor of a role of ultrasound techniques in the evaluation of bone mass and fracture risk, however their ability to monitor osteoporosis evolution of treatment is not widely established yet.  The relatively lower cost than DXA, the portability of the devices and the lack of radiation make QUS attractive for screening population in terms of fracture risk. QUS could be useful to mostly determine very low risk or high risk subjects, avoiding thus DXA measurements.

Other methods

From digitized plain radiographs of the hand and forearm, radiogrammetry software can provide an estimate of BMD, with a short-term precision error of less than 1%. Peripheral DXA (pDXA) devices have been developped to provide simpler and less expensive alternatives to DXA instruments scanning the central skeleton. Several regions in the forearm or the calcaneus are sites measured with pDXA.

Magnetic resonance imaging is a complex technique in which radiofrequency signals from hydrogen protons excited by high magnetic fields are recorded.. This non invasive and non ionizing technique provides tridimensional trabecular bone structure images by substraction from the signals generated by fat and water present in the bone marrow. Quantitative magnetic resonance imaging in the calcaneus can discriminate patients with and without vertebral deformities.

Though the evaluation of bone remodelling using serum or urinary biochemical markers could provide useful information on the rate of bone loss, on fracture risk, and on the response to antiosteoporotic therapies, the detemination of these markers does not replace the direct measurement of BMD.

REFERENCES

• Bates DW, Black DM, Cummings, SR. Clinical use of bone densitometry. Clinical applications. Jama 2002; 288: 1898-1900.

• Black DM, Cummings SR, Melton LJ. Appendicular bone mineral and a woman’s lifetime risk of hip fracture. J Bone Miner Res 1992; 7: 639-46.

• Blake GM, Fogelman I. Peripheral or central densitometry : does it matter which technique we use ? J Clin Densitom 2001 ; 4 :83-96.

• Blake GM, Knapp KM, Fogelman I. Absolute fracture risk varies with bone densitometry technique used. J Clin Densitom 2002; 5: 109-116.

• Bolotin HH, Sievänen H. Inaccuracies inherent in dual-energy X-ray absorptiometry  in vivo bone mineral density can seriously mislead diagnostic/prognostic interpretations of patient-specific bone fragility. J Bone Miner Res 2001 ; 16 :799-805.

• Bonnick SL, Johnston CC, Kleerekoper M, Lindsay R, Miller P, Sherwood L, Siris E. Importance of precision in bone density measurements. J Clin Densitom 2001; 4: 105-110.

• Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K et al. Bone density at various sites for prediction of hip fractures. Lancet 1993; 341: 72-5.

• Cummings SR, Palermo L, Browner W, Marcus R, Wallace R, Pearson J, Blackwell T, Eckert S, Black D, for the Fracture Intervention Trial Research Group. Monitoring osteoporosis therapy with bone densitometry. Misleading changes and regression to the mean. Jama 2000; 283: 1318-1321.

• Cummings SR, Bates D, Black DM. Clinical use of bone densitometry. Scientific review. Jama 2002; 288: 1889-1897.

• Dalen N, Hellstrom LG, Jacobson B. Bone mineral content and mechanical strength of the femoral neck. Bone mineral content and mechanical strength of the femoral neck. Acta Orthop Scand 1976; 47: 503-508.

• Dambacher MA, Neff M, Kissling R, Qin L.  Highly precise peripheral quantitative computed tomography for the evaluation of bone density, loss of bone density and structures.  Drugs & Aging 1988; 12 (suppl 1): 15-24.

• Faulkner KG, Cummings SR, Black D, Palermo L, Gluer CC, Genant HK. Simple measurement of femoral geometry predicts hip fracture: The study of osteoporotic fractures. J Bone Miner Res 1993; 8: 1211-1217.

• Faulkner KG, von Stetten E, Miller P. Discordance in patient classification using T-scores. J Clin Densitom 1999; 2:343-350.

• Faulkner KG. Bone matters : are density increases necessary to reduce fracture risk ? J Bone Miner Res 2000 ; 15 :183-187.

• Fournier PE, Rizzoli R, Slosman DO, Buchs B, Bonjour JP. Relative contribution of vertebral body and posterior arch in female and male lumbar spine peak bone mass. Osteoporos Int  1994; 4: 264-272.

• Genant HK, Engelke K, Fuerst T, Glüer CC, Grampp S, Harris ST, Jergas M, Lang T, Lu Y, Majundar S, Mathur A, Takada M. Noninvasive assessment of bone mineral and structure: State of the art. J Bone Miner Res. 1996; 11:707-730.

• Glüer CC for the International Quantitative Ultrasound Consensus Group.  Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status.  J Bone Miner Res 1997; 12: 1280-1288.

• Glüer CC. Monitoring skeletal changes by radiological techniques. J Bone Miner Res 1999; 14: 1952-1962.

• Hans D, Dargent-Molina P, Schott AM, Sebert JL, Cormier C, Kotzki PO, Delmas PD, Pouilles JM, Meunier PJ.  Ultrasonic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet 1996; 348:511-514.

• Jorgensen JT, Andersen PB, Rosholm A, Bjanarson NH. Digital X-ray radiogrammetry : a new appendicular bone densitometric method with high precision. Clin Physiol 2000 ;5 :330-335.

• Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D, on behalf of the European Foundation for Osteoporosis and Bone Disease Guidelines for diagnosis and management of osteoporosis.  Osteoporos Int  1997 7: 390-406

• Kanis JA, Devogelaer JP, Gennari C. Practical guide for the use of bone mineral measurements in the assessment of treatment of osteoporosis: A position paper of the European Foundation for Osteoporosis and Bone Disease. Osteoporos Int 1996; 6: 256-61.

• Kanis JA, Melton LJ, Christiansen C, Khaltaev N The diagnosis of osteoporosis.  J Bone Miner Res  1994 8: 1137-1141.

• Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report. Osteoporos Int 1994; 4: 368-81.

• Kanis JA, Torgerson D, Cooper C. Comparison of the European and USA pratice guidelines for osteoporosis. Trends Endocrinol Metab 2000; 11 :28-32.

• Kanis JA, Glüer CC. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporos Int 2000; 11 :192-202.

• Kanis JA, Johnell O, Oden A, Jonsson B, de Laet C, Dawson A. Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis. Bone 2000; 27: 585-590.

• Khan AA, Brown J, Faulkner K, Kendler D, Lentle B, Leslie W, Miller PD, Nicholson L, Olszynski WP, Watts NB, reviewed by Canadian Panel members Hanley D, Hodsman A, Josse R, Murray TM, Yuen K. Standards and guidelines for performing central dual X-ray densitometry from the Canadian Panel of International Society for Clinical Densitometry. J Clin Densitom 2002; 5: 247-257.

• Lang T, Augat P, Majumdar S, Ouyang X, Genant HK. Non-invasive assessment of bone density and structure using computed tomography and magnetic resonance. Bone 1998; 2 (suppl to no 5): 149-153.

• Li Y, Genant HK, Shepherd J, Zhao S, Mathur A, Fuerst TP, Cummings SR. Classification of osteoporosis based on bone mineral densities. J Bone Miner Res 2001 ; 16 :901-910.

• Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996; 312:1254-9.

• Melton LJ, Atkinson EJ, O’Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral assessed at different skeletal sites. J Bone Miner Res 1993; 8: 1227-33.

• Miller PD, Bonnick SL, Rosen CJ. Consensus of the international panel on the clinical utility of bone mass measurements in the detection of low bone mass in the adult population. Calcif Tissue Int 1996; 58:207-214.

• Miller PD, Zapalowski C, Kulak CAM, Bilezikian JP. Bone densitometry: the best way to detect osteoporosis and to monitor therapy. J Clin Endocrinol Metab 1999; 84:1867-1871.

• Nelson HD, Helfand M, Woolf SH, Allan JD. Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2002; 137: 529-541.

• Nguyen T, Pocock NA, Eisman JA. Interpretation of bone mineral density measurement and its changes. J Clin Densitom 2000 ; 3 :107-119.

• O'Neill TW, Lunt M, Silman AJ, Felsenberg D, Benevolenskaya LI, Bhalla AK, et al. The European Prospective Osteoporosis Study (EPOS) GROUP. The relationship between bone density and incident vertebral fracture in men and women. J Bone Miner Res 2002; 17:2214-2221.

• Orwoll ES, Oviatt SK, Biddle JA. Precision of dual-energy X-ray absorptiometry: development of quality control rules and their application in longitudinal studies. J Bone Miner Res. 1993; 8:693-699.

• Rizzoli R, Slosman D, Bonjour JP. The role of dual  energy X-ray absorptiometry of lumbar spine and proximal femur in the diagnosis and follow-up of osteoporosis. Am J Med 1995; 98 (suppl. 2A):33S-36S.

• Rolnick SJ, Kopher R, Jackson J, Fischer LR, Compo R. What is the impact of osteoporosis education and bone mineral density testing for postmenopausal women in a managed care setting? Menopause 2001; 8: 141-148.

• Sartoris D, Dalinka MK, Alazraki N, Berquist TH, Daffner RH, DeSmet AA, el-Khoury GY, Goergen TG, Keats TE, Manaster BJ, Newberg A, Pavlov H. Schweitzer ME, Haralson RH 3rd, McCabe JB. Osteoporosis and bone-mass measurement. American College of Radiology. ACR appropriateness criteria. Radiology 2000; 215 (suppl):397-414

• Slosman DO, Rizzoli R, Donath A, Bonjour JP. Vertebral bone mineral density measured laterally by dual-energy X-ray absorptiometry. Osteoporos Int 1990; 1: 23-29.

• Tosteson ANA, Rosenthal DI, Melton III LJ, Weinstein MC. Cost effectiveness of screening perimenopausal white women for osteoporosis: Bone densitometry and hormone replacement therapy. Ann Intern Med 1990; 113: 594-603.

• Varney LF, Parker RA, Vincelette A, Greenspan SL. Classification of osteoporosis and osteopenia in postmenopausal women is dependent on site-specific analysis. J Clin Densitom 1999 ; 2 :275-283.

• Wehrli FW, Hilaire L, Fernandez-Seara M, Gomberg BR, Song HK, Zemel B, Loh L, Snyder PJ. Quantitative magnetic resonance imaging in the calcaneus and femur of women with varying degrees of osteopenia and vertebral deformity status. J Bone Miner Res 2002; 17: 2265-2273.

• Weinstein RS. True bone strength. J Bone Miner Res 2000; 15:621-625.

• World Health Organisation (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis.  Technical Report Series 843, Geneve, WHO.

Table 1 : Characteristics of Different Bone Densitometry Techniques

 Table 2 : Relative Risk [95 % Confidence Interval] of Fracture for any 1 SD Decrease in areal Bone Mineral Density

From Marshall et al., 1996

Table 3: Life-time Risk of Hip Fracture (%) by Current Age and Femoral Neck BMD

Print this page

Edited by Aldo Campana,