Osteoporosis—An Overview1

An expert panel of the World Health Organization (WHO) established an operational diagnostic criteria for osteoporosis based on bone density, considering osteoporosis to be present when BMD levels in white women are more than 2.5 standard deviations (SDs) below the young normal mean. Women with a history of one or more fragility fractures are deemed to have severe osteoporosis. Osteopenia or low bone mass is defined by BMD levels as more than 1 SD below the young normal mean, but less than 2.5 SD below.² There is no established criteria for diagnosis of osteoporosis in non-white women, men and children.^7,8,9 Studies have shown that when bone size is taken into consideration, differences in bone density between men and women of different races are reduced.^3,10,11,12

The WHO criteria for osteoporosis have been useful for making public health and policy decisions for population and patient for whom no specific clinical information is available. The shortcoming of World Health Organization (WHO) criteria was that all osteoporosis patients need not have fractures and some skeletal sites are more predictive of fracture risk than others and also 2the measurement of BMD needs expensive equipment. Furthur, there is no clarity on the application of this diagnostic criteria for non-white women, men and children. With expanding knowledge of osteoporosis, various screening options like the scoring systems, biochemical markers, etc. emerge as accessible and cost effective means to screen, diagnose and manage osteoporosis.

Osteoporosis is distinct from Osteomalacia, in that the bone present is in reduced quality with normal mineralization. Bone loss commonly occur with aging, but osteoporosis can develop if a high peak bone mass is not achieved during adulthood. Osteoporosis is a chronic progressive disease with fractures as the most morbid clinical end point. In most cases, the disease is characterized by back pain from recurrent vertebral compressions, although fractures of distal tibia, hip, ribs or wrist can be the initial presentation. Vertebral fractures can cause back pain, height loss, or spinal deformities such as kyphosis. Hip fractures are associated with substantial morbidity and mortality.⁴

The most important causative factors responsible for local bone loss are immobilization and transient osteoporosis as seen in pregnancy and postpartum period. These are self limiting and recover completely.

Generalized osteoporosis rarely manifests in the entire skeleton and are of two types—primary and secondary. Osteoporosis is classified as primary which includes postmenopausal (Type I) and senile osteoporosis (Type II), secondary osteoporosis which is secondary to specific causes.⁶ However, this distinction overlaps, for individuals with secondary osteoporosis are more likely to fracture when they have primary osteoporosis.

The type I (Fig. 1.1) variety occurs typically between 55–75 years, affects mainly trabecular bone and is more common in women than in men (6:1 ratio). This is basically due to cessation of ovarian function. Prior to menopause, bone loss occurs at the rate of 0.5% to 1.0% per year. At menopause, bone loss accelerates at the rate of 2% to 5% per year due to decline in estrogen levels and is greatest in the first 3–6 years postmenopause.

The type II or age-related osteoporosis occurs after the age of 70 years, affects both cortical and trabecular bone and affects women twice as frequently as men (Fig. 1.2). This may be attributed to the process of aging with increased osteoclastic activity and other factors are immobility, mild secondary hyperparathyroidism, calcium and vitamin D deficiency. Irrespective of the type of osteoporosis, identifying etiologic factors that adversely affect the basic multicellular unit and thereby increase an individual's risk for fracture will remain a major goal, both in the prevention and treatment of osteoporosis. Feature of primary osteoporosis type I and type II are given in Table 1.1 and causes are elaborated in Table 1.2.

It is called “high turnover” when there is increased osteoclastic activity without increased osteoblastic activity, “low turnover” when there is normal osteoclastic but decreased osteoblastic activity, decreased osteoclastic and osteoblastic activity indicates “atrophy”. Estrogen deficiency increases the high turnover, increases the lifespan of osteoclasts and promotes osteoblastic apoptosis. Reduced vitamin D-hormone (1,25-(OH)2D3) synthesis in the kidney, because of decreased activity of the 1α hydroxylase enzyme, is a pathogenic cofactor in postmenopausal osteoporosis. Increased calcium release from bone and concomitant parathyroid hormone (PTH) suppression are primarily responsible for this and additionally, estrogen is also an important cofactor in the activation of 1 α hydroxylase. Two important factors in renal vitamin D activation, namely PTH and estrogen levels, are reduced after menopause and thus explain in part calcium malabsorption and suppression of other vitamin D hormone effects. A deficiency in vitamin D receptors (VDRs) in the intestines and in bone is evident; this deficiency with regard to the number and activity of the receptors, is dependent on the estrogen deficiency.⁶

High and low turnover activity coupled with negative bone balance lead to countless perforations or breaks of the trabecula leading to the “micro fractures”, or “fatigue damage” (Fig. 1.3) which occurs constantly and which together with the thickness of the bones determine the fracture risk. As these tiny fractures accumulate, they weaken older bones and contribute to fracture risk if not quickly and adequately repaired. This, in addition to a slightly negative bone balance over time, eventually leads to reduction in structural continuity of the trabecular network and thereby loss of strength. Micro fractures are not detected by standard X-rays but by special microscopic techniques in bone biopsies. Since osteoporosis is asymptomatic, the first clinical presentation may be a fracture. Diagnosis is based on measuring the bone mass, an indirect way of studying skeletal health.

Osteoporosis in elderly patients of both sexes is characterized by uncoupled bone remodeling (decreased bone formation with, to a certain extent, increased bone resorption). This uncoupling is induced by sex hormone deficiencies (estrogen or testosterone), by the so-called somatopause (growth hormone or insulin like growth factor 9 IGF deficiency), by vitamin D deficiency and importantly, by reduced synthesis of vitamin D-hormone in kidneys and bones by 1a hydroxylase deficiency. It is also induced by the lack of receptors or receptor affinity for vitamin D-hormone in the target organs (gastrointestinal tract bones and parathyroid).

Hence, in clinical practice, the diagnosis of osteoporotic fracture is also a diagnosis of exclusion. For example, traumatic fractures in childhood and adolescence are nonosteoporotic; these include skull fractures among infants and long bone fractures adolescents. Another class of nonosteoporotic fractures are occupation-related fractures, frequently involving the hands and feet.

Risk factors are derived by history and clinical examination. The gold standard for obtaining the BMD is DEXA. It is important to distinguish between risk factors for osteoporosis as defined by BMD (both primary and secondary) and clinical risk factors for osteoporotic fractures.

Fractures at any site are of clinical concern, since prior fractures can lead to subsequent fractures:

Common sites of fracture are vertebrae, hip or neck of hip, humerus wrist and ankle.

The interpretation of radiograph has traditionally been visual. Vertebral fractures have been classified as crush, wedge and end-plate. More recently, quantitative vertebral morphometry has been employed.

Substantial vertebral height reductions usually represent a fracture, but there may be some measurement error involved. Some studies defined a new fracture as a ≥15% reduction in any one of the three measured heights (Ha, Hm, Hp).