Osteoporosis problem grows with world’s aging population

Osteoporosis problem grows with world’s aging population

Tom Clark

LUXEMBOURG – Increasing longevity in most developed countries is bringing about a rapid rise in the number of people at risk for osteoporosis and subsequent fractures, particularly of the femur and of spine deformations. Of every, 100 white post-menopausal women, 54 are osteoponic and 30 are osteoporotic. This means that in the United States alone there are 26 million women at risk. In the U.S., there are an estimated 500,000 cervical spine compressions each year and 270,000 femoral fractures.

Bone density is the main measurable determinant in assessing osteoporotic fracture risk. Bone density increases during infancy and adolescence, reaching a peak three years after puberty and thereafter diminishing. Adult women have less skeletal bone than men at all ages, and suffer a post-menopausal bone loss which can be substantial. Normally bone loss is on the order of 0.3% to 0.5% per year, but can increase to 5% to 6% annually in some women during the 5 years after menopause. As a result, women can lose 30% to 40% of their maximum bone mass, while men will lose only 20% to 30%.

The determination of bone mass, the measurement of annual bone loss, and with women, the measurement of post-menopausal loss all contribute toward assessment of osteoporotic risk. But there are a number of other significant factors that can also have an effect (Table 1 on page 170). The widely accepted view that only older women are at risk for osteoporosis is an oversimplification, with many other significant factors playing a role.

Of fractures and associated complications associated with osteoporosis, the most typical are fractures of the neck of the femur, forearms and vertebral compression, although almost all sites are possible. Femoral fractures are the most important in terms of morbidity, with 5% to 20% of patients dying within one year and more than 50% handicapped for life.

Causes of osteoporosis

The regulation of bone metabolism, which results in either the formation or the resorption of bone mass, is very complex and involves numerous other partners such as hormones, growth factors, cytokines, etc.

In post-menopausal osteoporosis, the bone mass loss varies from one woman to another and arises as a result of a fall in estrogen production. With senile osteoporosis (Table 2), the mechanism is associated with a fall in osteoblast activity and in addition a negative calcium balance of multiple origins. Secondary osteoporosis can arise as a result of another medical problem or as a consequence of a specific therapy. These osteoporoses are often reversible, however, following removal of the causative factor.

Ultrasound bone density assessment

Based on numerous studies which have confirmed the relationship between bone mass and fracture risk, the number of bone density measurement modalities has expanded from X-ray to include computer tomography (CT), dual energy X-ray absorbtiometry (DEXA) and most recently ultrasound.

CT measures true density and has the advantage of being able to measure separately trabecular and cortical bone mass, particularly useful in vertebral measurements. [TABULAR DATA FOR TABLE 2 OMITTED] DEXA is widely used where repeat measurements of bone density are indicated, such as postmenopausal, where it is important to identify “fast losers” as soon as possible. Ultrasound is rapid and has significantly lower cost than DEXA, making it particularly interesting for use in physicians’ offices.

The number of suppliers in the osteoporosis test sector is increasing (Table 3 on page 171) so that the major DEXA suppliers, Hologic (Waltham, Massachusetts), Lunar (Madison, Wisconsin) and Norland (Fort Atkinson, Wisconsin) have been joined by three Japanese suppliers, Aloka, Chugai and Fuji (all Tokyo), as well as Scanco Medical (Basserdorf, Switzerland). A major block to a wider use of DEXA screening has in the past been speed and high installation cost. As a result, many women with osteoporosis remain undiagnosed. Ultrasound is widening the potential market by moving osteoporosis screening into the physician’s office.

In Europe, ultrasound osteoporosis screening increasingly is being offered by gynecological specialists as part of their post-menopausal hormone therapy follow-up.

Lunar, a major DEXA supplier, launched its Achilles U/S densitometer in Europe at the giant Medica show nearly two years ago. Hologic, another major player in the DEXA sector, also has moved into the European ultrasound sector with its Sahara portable densitometer. An FDA advisory panel recently recommended marketing approval in the U.S. for the Sahara, albeit with some reservations. If the Sahara is recommended by FDA, it will be the first densitometer marketed in the U.S. that does not use ionizing radiation. Other ultrasound densitometers also available in Europe are from DMS (Montpellier, France), McCue (Compton Winchester, England) and Myriad Ultrasound (Rhovoth, Israel).

Clinical diagnostics in osteoporosis

In recent years a number of bone formation and bone resorption marker tests have been developed which have augmented traditional clinical laboratory assays for calcium, ionized calcium (by blood gas analyser), parathyroid hormone, calcitonin and phosphates. Most commercialized marker assays (Table 4) have been for bone resorption and include tests for free pyridinolines (Metra Biosystems and Chiron Diagnostics), cross-linked N-telopeptide (Ostex International and Ortho Clinical Diagnostics), C-telepeptide (CIS bio international and Osteometer) and crosslinked C-telopeptide (Orion Diagnostika). Boehringer Mannheim (Mannheim, Germany) and Sequana Therapeutics (La Jolla, California) have a joint research program under way to investigate development of genetic testing for osteoporosis.

Osteoporosis and increased cardiovascular risk

A recently published study by Christian Hassager and his group at the Center for Clinical and Basic Research (Ballerup, Denmark) has shown that low bone mineral content at menopause in otherwise healthy women is not only a risk factor for future fractures, but also a risk factor for cardiovascular death.

The group followed up more than 1,000 women for up to 17 years and found that in 50-year-old women, low bone mass was an even stronger predictor of future cardiac death than traditional factors such as serum cholesterol and cigarette smoking. In addition, elderly women who experience a spinal fracture (crushed vertebral body which occurs spontaneously in osteoporotic women) have about a 50%, increased risk of dying from cardiovascular disease.

Table 3

Bone Mass Measurement Techniques

Technology Selected Suppliers

Computed Philips Medical (Best, the Netherlands)

Tomography Siemens (Erlangen, Germany)

(CT) Stratec (Birkenfeld, Germany)

Toshiba (Tokyo)

Dual Energy X-ray Aloka (Tokyo)

Absorbtiometry Chugai (Tokyo)

(DEXA) Fuji (Tokyo)

Hologic (Waltham, Massachusetts)

Lunar (Madison, Wisconsin)

Norland (Fort Atkinson, Wisconsin)

Scanco Medical (Basserdorf, Switzerland)

Ultrasound DMS (Montpellier, France)

(U/S) Hologic

Lunar

McCue (Compton Winchester, England)

Myriad Ultrasound (Rehovoth, Israel)

Source: The BBI Newsletter

[TABULAR DATA FOR TABLE 4 OMITTED]

The Danish researchers’ recommendations include suggestions that since evaluation of patients for cardiovascular disease often include a chest X-ray, further X-rays to detect crushed vertebral bodies should be included. They also said that low bone mineral content in women should be a marker for increased cardiovascular risk and that hormone replacement therapy post-menopause may have beneficial cardiovascular as well as osteoporotic effects.

Table 1

Osteoporosis Risk Factors

Age: Each decade is associated with an increase of risk of x 1.4 to 1.8.

Genetic

* Ethnic: Maximum risk for whites, Asiatics. Minimum risk for blacks, Polynesians.

* Sex: Higher risk in women.

* Family history of osteoporosis.

* Small skeletal frame.

Environmental

Nutritional

* Low calcium regime

* Milk intolerance

* High animal protein regime

* Vegetarian

* Anorexia

Lifestyle

* Alcoholism

* Lack of exercise

* Smoking

* Excessive exercise

Physiological factors

* Multiple pregnancies

* Extended confinement to bed

* Late puberty

* Early menopause

Medical

Secondary osteoporosis can arise with diseases such as early hyperparathyroiditis, Cushings disease, mental anorexia, etc. Also it can arise with some drugs; e.g. thyroid hormones, corticosteroids, heparin, lithium, anticonvulsives, etc.

Source: Jean-Christian Souberbielle, Hopital Edouard Herriot (Lyon, France)

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