Osteoporosis is accelerated bone loss. Normally, there is loss of bone mass with aging, perhaps 0.7% per year in adults. However, bone loss is greater in women past menopause than in men of the same age. The process of bone remodeling from resorption to matrix synthesis to mineralization normally takes about 8 months--a slow but constant process. Bone in older persons just isn't as efficient as bone in younger persons at maintaining itself--there is decreased activity of osteoblasts and decreased production of growth factors and bone matrix.
(Sambrook and Cooper, 2006)
This diagram illustrates changes in bone density with aging in women. The normal curve (A) steepens following menopause, but even by old age the risk for fracture is still low. A woman who begins with diminished bone density (B) even before menopause is at great risk, particularly with a more accelerated rate of bone loss. Interventions such as postmenopausal estrogen (with progesterone) therapy, the use of drugs such as the non-hormonal compound alendronate that diminishes osteoclast activity, and the use of diet and exercise regimens can help to slow bone loss (C) but will not stop bone loss completely or restore prior bone density.
Diet and exercise have a great benefit in younger women to help build up bone density and provide a greater reserve against bone loss with aging. (Winslow et al, 2009)
The World Health Organization (WHO) has defined osteoporosis as a spinal or hip bone mineral density (BMD) that is 2.5 standard deviations or more below the mean BMD for healthy, young women, measured by dual energy x-ray absorptiometry (DEXA). The WHO defines osteopenia as a spinal or hip BMD between 1 and 2.5 standard deviations below the mean for healthy, young women. (Sweet et al, 2009)
Fracture risk can be estimated at: http://osteoed.org/tools.php
Bone metabolism is controlled by a variety of factors.

Parathyroid hormone receptors are found on osteoblasts. Parathyroid hormone (PTH) stimulation of osteoblasts increases osteoblast production of receptor activator of nuclear factor kappa-B ligand (RANKL). Hematopoietic cell precursors stimulated by M-CSF give rise to osteoclasts that express RANK receptor. The RANKL/RANK interaction stimulates differentation of the osteoclasts so that they can resorb bone. Osteoblasts also produce a decoy receptor called osteoprotegerin (OPG) that binds to RANKL and prevents the
RANKL/RANK interaction.
Estradiol increases production of OPG to diminish bone resorption. Glucocorticoids stimulate
RANKL expression while inhibiting OPG synthesis by osteoblasts to enhance osteoclast proliferation and differentiation, leading to bone resorption. (Vega et al, 2007) (Romas, 2009)
Risk factors for osteoporosis include:
 Female sex
 Age > 70 years
 Caucasian or Asian race

 Early onset of menopause
 Longer postmenopausal interval
 Inactivity, especially lack of weight bearing exercise
Osteoporosis can be classified as primary or secondary. Primary osteoporosis is simply the form seen in older persons and women past menopause in which bone loss is accelerated over that predicted for age and sex. Secondary osteoporosis results from a variety of identifiable conditions that may include: (Sweet et al, 2009)
 Metabolic bone disease, such as hyperparathyroidism
 Neoplasia, as with multiple myeloma or metastatic carcinoma


Malnutrition
 Drug therapy, as with corticosteroids
Prolonged immobilization
 Weightlessness with space travel
Modifiable risk factors that may potentiate osteoporosis include:
1. Smoking
2. Alcohol abuse
3. Excessive caffeine consumption
4. Excessive dietary protein consumption
5. Lack of dietary calcium
6. Lack of sunlight exposure (to generate endogenous vitamin D)
Diagnosis of osteoporosis is made by three methods:
1. Radiographic measurement of bone density
2. Laboratory biochemical markers
3. Bone with pathologic assessment
Of these three the best is radiographic bone density measurement. A variety of techniques are available, including single-photon absorptiometry, dual-photon absorptiometry, quantitative computed tomography, dual x-ray absorptiometry, and ultrasonography. Most often, site specific measurements are performed. The most common sites analyzed are those with greatest risk for fracture: hip, wrist, and vertebrae. The forearm and heel that are easily measured using single-photon absorptiometry, quantitative computed tomography, and ultrasonography can be inexpensive, but these sites are typically unresponsive to therapy and give less information about response to therapy. Increased risk for fracture correlates with decreasing bone density. Serial measurements over time can also give an indication of the

rate of bone loss and prognosis (Bonnick and Shulman, 2006).
Biochemical markers for bone turnover include bone alkaline phosphatase, osteocalcin in serum and.deoxypyridinoline and pyridinoline in urine. (Bonnick and Shulman, 2006) (El
Maghraoui and Roux, 2008)
 Alkaline phosphatase, which reflects osteoclast activity in bone, lacks sensitivity and specificity for osteoporosis, because it can be elevated or decreased with many
 diseases. It is increased with aging. Fractionating alkaline phosphatase for the fraction more specific to bone doesn't increase usefulness that much.
Osteocalcin, also known as bone gamma-carboxyglutamate. It is synthesized by osteoblasts and incorporated into the extracellular matrix of bone, but a small amount is
 released into the circulation, where it can be measured in serum. The levels of circulating osteocalcin correlate with bone mineralization, but are influenced by age, sex, and seasonal variation. Laboratory methods also vary.
The bone resorption markers in urine are breakdown products of type I collagen and include pyridinium crosslinks known as pyridinoline and deoxypyridinoline. They reflect bone remodeling but not the status of bone mineral density.
Bone biopsy is not often utilized for assessment of bone density. This test has limited availability, and is most often performed as a research technique for analysis of treatment regimens for bone diseases. Bone biopsy involves double tetracycline labelling to determine appositional bone growth. Doses of tetracycline are given weeks apart, and the bone biopsy is embedded in a plastic compound, sliced thinly, and examined under fluorescent light, where the lines of tetracycline (which autofluoresce) will appear and appositional growth assessed.
Osteomalacia, for example, has diminished appositional growth. (Malluche et al, 2007)
Osteoporotic bone is histologically normal in its composition--there is just less bone. This results in weakened bones that are more prone to fractures with trauma, even minor trauma.
The areas most affected are:
 Hip (femoral head and neck)
 Wrist
 Vertebrae
Hip fractures that occur, even with minor falls, can be disabling and confine an elderly person to a wheelchair. It is also possible to surgically put in a prosthetic hip joint. Wrist fractures are common with falls forward with arms extended to break the fall, but the wrist bones break too.
Vertebral fractures are of the compressed variety and may be more subtle. Vertebral fractures may result in back pain. Another consequence is shortening or kyphosis (bending over) of the spine. This can lead to the appearance of a "hunched over" appearance that, if severe

enough, can even compromise respiratory function because the thorax is reduced in size.
Persons suffering fractures are at greater risk for death, not directly from the fracture, but from the complications that come from hospitalization with immobilization, such as pulmonary thromboembolism and pneumonia.
Osteoporosis is so common that, on average, about 1 in 2 elderly Caucasian women will have had a fracture. In contrast, only about 1 in 40 men of similar age will have had a fracture. Men start out with a greater bone mass to begin with, so they have a greater reserve against loss.
However, that is still a large number of men with osteoporosis. (Binkley, 2009)