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.

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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

BMD T-Score	Age
	50 yrs	60 yrs	70 yrs	80 yrs
- 4	69 %	62	54	36
- 3	48	40	31	18
- 2	29	21	15	8
- 1	16	11	7	3
0	8	5	3	1
+ 1	4	2	1	<1