Definition

Osteoporosis is 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.

An international conference, held in 1993 to develop a common framework for a better understanding of the diagnosis, prophylaxis, and treatment of osteoporosis, established a definition for osteoporosis to educate physicians and the public about the disease and to improve diagnosis [Anon, 1993]. The above consensus was not intended to define a treatment threshold for osteoporosis.

In other words, osteoporosis is a disease generally affecting the entire skeleton in which the overall mass of bone is decreased and the structure of the bone is damaged. The term "microarchitectural deterioration" refers to the thinning of the trabeculae and the loss of intertrabecular connections in bone. These changes in bone mass and structure reduce the overall strength of the bone and make it prone to fracture.

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture.

The above definition for osteoporosis was provided to educate physicians and the public about this disease at an international conference held in 2000. This conference was convened to further the understanding of, and to try and improve the diagnosis, prophylaxis, and treatment of, osteoporosis [National Institutes of Health, 2000]. Bone strength is affected by two main factors: bone density and bone quality. Osteoporosis can be regarded either as a silent, systemic disease or as a progressive risk factor for fracture. The clinical manifestation of the systemic disease of osteoporosis is fracture.

Most X-ray technology is not capable of detecting bone loss (radiographic osteopenia) until at least 30% of bone mass is lost [World Health Organization (WHO) Study Group, 1994]. Therefore, osteoporosis is commonly diagnosed in a patient seeking treatment in an emergency department (or physician's office) for a symptomatic osteoporotic vertebral or hip fracture. However, a vertebral fracture may be asymptomatic, in which case the fracture may be diagnosed later as an incidental finding when the patient gets an X-ray for another complaint. Standard X-rays are useful in confirming the diagnosis of fractures.

The most vulnerable sites of fracture — and the three principal sites of osteoporotic fractures — are the hip, vertebrae, and wrist (see figure below).

Three Principal Sites of Osteoporotic Fractures

Click on image for animation/larger version.

With the technologies developed over the past several years, such as bone densitometry, a patient's bone mass or bone mineral density (BMD) can be determined. BMD refers to grams of bone mineral — specifically hydroxyapatite — per square centimeter of bone cross-section and is expressed in units of g/cm². However, the technology is limited because BMD is a two-dimensional image of a three-dimensional object.

T-Score and Z-Score

A patient's BMD, measured by densitometry and expressed in g/cm², is compared with a "normal value." The normal value is the mean BMD of sex-matched young adults at their peak bone mass, sometimes referred to as the "young adult mean." When compared with the normal value, a patient's BMD can be expressed in terms of the number of standard deviations (SD) from the normal value. A convenient way to express this is a T-score. The Z-score normalizes a patient's BMD in a different way, by comparing the amount of bone loss with the expected loss for individuals of the same age and sex.

Classification

Osteoporosis can be classified in various ways based on diagnostic categories, etiology, or stage to help clinicians manage their patients. These classifications include the WHO classification, classification as either primary osteoporosis or secondary osteoporosis, and the Mayo Clinic classification.

WHO Classification

For purposes of demographics and prevalence estimates, WHO classified patients according to BMD values and published the information in 1994 [WHO Study Group, 1994]. The intended use for the classification was to compare the prevalence of osteoporosis in various countries. These reference ranges are based on population distributions and were not specifically developed for clinical decision-making in the treatment of individual patients. Nevertheless, the WHO classification system is commonly referred to in the literature and in discussions of bone disease.

According to the WHO Study Group, the general diagnostic categories are:

• Normal: BMD or bone mineral content (BMC) not more than 1 SD below the young adult mean (T-score above -1).
• Osteopenia (or low bone mass): BMD or BMC between 1 and 2.5 SD below young adult mean (T-score between -1 and -2.5).
• Osteoporosis: BMD or BMC 2.5 SD or more below the young adult mean (T-score at or below -2.5).
• Severe osteoporosis (or established osteoporosis): BMD or BMC 2.5 SD or more below the young adult mean in the presence of one or more fragility fractures.

Although WHO defined osteoporosis as BMD 2.5 SD or more below the young adult mean, the following categories were commonly used:

• Osteopenia was defined as bone mass that is more than 1 SD but less than 2 SD below the young adult mean bone mass.
• Osteoporosis was defined as bone mass that is 2 SD or more below the young adult mean bone mass.

Primary Osteoporosis vs. Secondary Osteoporosis

Osteoporosis can be classified as a primary or secondary disease.

• Primary osteoporosis is the most common form of osteoporosis and is diagnosed when other disorders known to cause osteoporosis are not present. Primary osteoporosis is also classified according to age groups.

• Juvenile osteoporosis affects prepubescent boys and girls.
• Idiopathic osteoporosis describes the condition in young adults when the cause is not related to another disease.
• Postmenopausal osteoporosis occurs in women within 15-20 years after menopause.
• Age-related, or senile, osteoporosis describes the disease in the elderly.

• Secondary osteoporosis is diagnosed when the condition is related to another illness or to the use of medications or drugs. Various factors can contribute to secondary osteoporosis (see table below).

Factors Contributing to Secondary Osteoporosis

Congenital Conditions	Homocystinuria; hemolytic anemia; hypophosphatasia; osteogenesis imperfecta
Diet	Anorexia nervosa; calcium deficiency; malabsorption syndromes; scurvy; starvation
Drugs	Alcohol; anticonvulsants; cancer chemotherapy; excess thyroid hormone; glucocorticoids; heparin
Endocrine Disorders	Cushing's syndrome; growth hormone deficiency; hypercortisolism; hyperparathyroidism; hyperthyroidism; hypogonadism
Other Systemic Disorders	Diabetes mellitus; leukemia; mastocytosis; multiple myeloma; renal tubular acidosis; rheumatoid arthritis

Mayo Clinic Classification

Researchers at Mayo Clinic suggested that primary osteoporosis be classified as Type I or Type II osteoporosis [Riggs and Melton, 1986].

• Type I — postmenopausal osteoporosis — affects women after menopause and is associated with wrist fractures and vertebral crush fractures.
• Type II — age-related, or senile, osteoporosis — affects men and women older than age 70 and is associated with hip fractures and vertebral wedge fractures.

The following table compares Type I and Type II osteoporosis.

Comparison of Type I and Type II Osteoporosis

Factors	Type I Postmenopausal Osteoporosis	Type II Age-Related, or Senile, Osteoporosis
Age	55-75	>70
Sex (F:M ratio)	6:1	2:1
Fractures	Wrist and vertebra	Hip and vertebra

Each type of osteoporosis may have a different cause. Type I occurs in women who have high levels of postmenopausal bone loss and is thought to result primarily from the estrogen-deficient state that occurs after menopause (see figure below). In Type I osteoporosis, trabecular (cancellous) bone is preferentially decreased. This causes women to become prone to crush fractures of the vertebrae or Colles' fractures of the wrist if they happen to fall.

Postmenopausal Bone Loss

From Stepan et al. [1987]; with permission.
Click on image for larger version.

Estrogen deficiency in early postmenopausal women can accelerate bone loss for one of two reasons:

• Bone resorption exceeds bone formation at each bone remodeling unit (BMU), resulting in net bone loss (see figure below).
• The rate of bone turnover increases, meaning that the number of active BMUs increases.

Increasing Bone Resorption and Net Bone Loss

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Women are at risk for Type I osteoporosis because their bone loss after menopause is significantly greater than bone loss in men at comparable ages. During the first 5-7 years after menopause, women experience a rapid decline in bone mass due to an increased rate of bone turnover secondary to loss of ovarian estrogen production. The estimated rate of bone loss at this time in a woman's life is 2-3% per year (e.g., 10-15% during first 5 years immediately after menopause). It is not uncommon for women to lose 3-5% per year for the first 5-7 years after menopause [National Institutes of Health, 2000]. Generally, bone mass declines at a lower rate thereafter, although the rate of bone turnover may remain elevated for the entire duration of postmenopausal life, as depicted in the figure below.

Pattern of Bone Loss with Age in Men and Women

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Over their lifetimes, women lose about 30-50% of their total bone mass [Riggs et al., 1981], as depicted in the figure below.

Bone Loss in Women during Adult Life

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Type II osteoporosis is a universal phenomenon. Age-related changes result in a reduction of both trabecular and cortical bone mass. Trabecular bone loss occurs in both men and women but the pattern is different. In men, there is a trabecular thinning, whereas in women the thinning can progress to very deep resorption cavities at certain sites, resulting in a loss of connections between the trabecular plates, or trabecular perforation (see figure below).

Patterns of Trabecular Bone Loss

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Trabecular connectivity is necessary for bone strength. Once these intertrabecular connections are broken, they cannot be restored; the microarchitecture is permanently altered.

By age 80, most individuals have experienced sufficient femoral bone loss to put them at risk for hip fractures. Bone loss with aging may also cause additional vertebral wedge fractures and gradual deformation of the spine (see figure below). The exact cause of Type II osteoporosis is not yet known but is believed to be multifactorial.

Loss of Bone Density with Age in Spine, Hip, and Wrist

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Although estrogen deficiency is the major cause of bone loss in postmenopausal women, other age-related factors can contribute to bone loss in both women and men. These factors include:

• age-related reduction in osteoblast activity, which results in a reduction in bone formation
• decreased calcium absorption with increasing age, possibly from decreased vitamin D intake and synthesis
• reduced dietary intake of calcium
• hyperparathyroidism — probably secondary to decreased calcium absorption — which contributes to increased bone turnover and bone loss
• low levels of circulating testosterone, in men, and possibly estrogen deficiency relative to other men without osteoporosis.

References

Anonymous. Consensus Development Conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993;94:646-650.

National Institutes of Health. Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consensus Statement 2000. March 27-29;17:1-36.

Riggs BL, Melton LJ III. Involutional osteoporosis. N Engl J Med. 1986;314:1676-1686.

Riggs BL, Wahner HW, Dunn WL, et al. Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981;67:328-335.

Stepan JJ, Pospichal J, Presl J, et al. Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women. Bone. 1987;8:279-284.

WHO Study Group on assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Report of a WHO Study Group. WHO Technical Report Series 843; 1994.

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