Block 2 Pathology Test 1 Chapter 7 Osteoporosis

What are the three grades of vertebral fractures?

(A) Biconcave fractures. Biconcave fractures cause depression of the upper and lower endplates of the vertebral bodies. They are the first to appear. (B) Anterior wedging. Anterior wedging occurs next producing a loss of the vertebral body height >50%. (C) Compressive (crush) fracture. The last type to occur is the compressive (crush) fracture, which results in vertical compression of the entire vertebral body.

How does menopause affect osteoporosis?

(A) Type I osteoporosis. This is an accelerated phase of bone loss than begins at menopause and results in a loss of disproportionately more cancellous bone than compact bone. Menopause is characterized by a marked decrease in estrogen serum levels. Estrogens prevent bone loss by two mechanisms: (a) pro-apoptotic effects on osteoclasts and (b) anti-apoptotic effects on mature osteoblasts and osteocytes. The large and rapid decrease in estrogen secretion at menopause leads to increased bone turnover. Bone resorption increases to a greater extent than does bone formation leading to rapid bone loss. However, although all postmenopausal women are estrogen deficient, type I osteoporosis occurs in about 5%-20% of them. The rates of the wrist, spine and hip fractures increase after menopause.

What is the clinical presentation of osteoporosis?

1. Back pain. The most frequent reason for seeking medical attention is back pain, indicating a vertebral crush fracture. Pain is sudden and worse on movement, relieved by rest. The majority (~80% or more) of vertebral crush fractures cause no pain and are discovered incidentally after a routine radiograph reveals the deformities. 2. Chronic dull back ache. Spinal osteoporosis that does not present as an acute fracture is often accompanied with a chronic dull back ache. The pain is often difficult to localize accurately. 3. Loss of height or kyphosis. Others seek medical care when they become concerned about loss of height or kyphosis (i.e., excessive convexity of the thoracic spine, resulting in humpback), both outcomes of multiple vertebral fractures. Thoracic kyphosis is a consequence of the collapse of the thoracic vertebrae (dowager's hump). 4. Unsure gait. Walking becomes slow and unsure (because the body's center of gravity is displaced forward) with small steps to avoid transmitting shocks to the vertebral column.

What are risk factors for osteoporosis? There are 12

1. Genetics. A family history of an osteoporotic fracture in a first-degree relative is a risk factor. 2. Race. Caucasians tend to have the lower bone mass and hip fractures are far more common among whites than nonwhites. African American women tend to have the highest bone density and lose bone less rapidly as they age. 3. Sex. Osteoporosis is more common in women than in men 4:1 4. Age. Before 35 years of age, bone resorption and formation are balanced. After the age of 35 years women tend to lose bone mass at a rate of 0.5-1.0% per year. 5. Previous fractures. A fracture raises the risk of further fracture by a factor of 2. 6. Pregnancy and lactation. There is a temporary decrease in bone density during pregnancy and breast feeding. 7. Chronic physical inactivity. Insufficient physical movement is the single most important risk factor for osteoporosis. 8. Low body weight: ('slim women-thin bones'). Underweight women have a risk of fractures, while overweight women are rarely affected by osteoporosis. 9. Cigarette smoking. Smoking doubles the risk of osteoporosis. 10. Nutritional deficiency. Healthy bones require healthy eating habits. Specifically calcium, phosphorus, vitamin D, C, K, B6, B12, and folic acid. 11. Early menopause. An early menopause is an important risk factor. 12. Medications. Many drugs weaken bone: the most important are cortisone and its derivatives.

What three things define osteoporosis?

1. Low bone mass. Osteoporosis is a skeletal condition characterized by low bone mass, which is associated with reduced bone strength and an increased risk of fractures. The measurement of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) is used as an index of bone mass, bone strength and fracture risk, and can be used to diagnose osteoporosis in some populations, such as postmenopausal women. The WHO defines osteoporosis in postmenopausal women as a BMD value at the spine, hip, or forearm of 2.5 or more SD (standard deviations) below the young adult mean (T-score ≤-2.5), with or without the presence of a fragility fracture. 2. Quality of osteoporotic bone. Grossly and histologically, bones demonstrate increased porosity. Bone tissue is normally mineralized but is present in reduced quantity. The decrease in bone mass is clinically manifested with skeletal fragility (the lower the bone mass, the weaker the bone) and increased risk of fractures. 3. Low trauma fracture. Bone fractures are the only clinical manifestation of osteoporosis. When bone strength is sufficiently weak, fractures that occur from a standing height or less, without major trauma such as a motor vehicle accident, can be considered a low-trauma or fragility fracture.

BMD definitions of normal bone, osteopenia, and osteoporosis.

1. Normal bone. Bone mineral density (BMD) results are reported as T score or Z score, not in absolute units. A normal bone mineral density (BMD) is defined as a value less than 1 standard deviation below the young adult mean value. This corresponds to T score: negative 1.0 (or - 1.0) 2. Osteopenia (or borderline osteoporosis). Osteopenia is defined as a BMD from negative 1.0 (- 1.0) down to negative 2.5 (- 2.5) standard deviations (SD) below the reference range. Patients with osteopenia are in no urgent need of therapy, which can be given without haste and monitored by BMD measurements. Years may elapse before fractures occur in this group in the absence of preventive therapy. 3. Preclinical osteoporosis. This is defined as a BMD that is at least or more than 2.5 standard deviations below the mean. Fractures have not yet occurred but could do so at any time. There is no time to lose, so effective antiresorbtive therapy should be administered immediately. An aminobisphosphonate is the drug of choice. 4. Established (severe, manifest) osteoporosis. Severe osteoporosis is defined as a BMD value of more than 2.5 standard deviations below the young adult mean value in the presence of 1 or more fragility fracture.

What are the radiographic features that suggest osteoporosis on lateral radiographs of the spine?

1. Verticalization. Loss of trabecular bone occurs in a predictable pattern. The non-weight bearing (horizontal) trabeculae are resorbed first. This leads to a relative prominence of the weight-bearing (vertical) trabeculae. 2. Picture frame. With decreasing density, the trabecular bone becomes increasingly radiolucent and the cortical rim of the vertebrae becomes more accentuated. Therefore, the vertebrae may have a "picture frame" appearance. 3. Thinning of the cortical bone. Thinning of the cortical bone occurs in addition to changes in the trabecular bone, and the cortices appear paper thin.

What are high-energy and low-energy fractures?

A fracture is an "acute discontinuity" in a bone as a result of physical trauma. Fracture incidence in the community is bimodal, with peaks in youth and advanced age. In young people, fractures of the long bones following major trauma predominate, and the incidence is greater in young men than in young women. Major trauma results in a "high energy" fracture. After the age of 50 years, overall fracture incidence climbs steeply. Over 80% of all fractures in people older than 50 years are caused by osteoporosis. Osteoporotic fractures are considered fragility fractures. These fractures typically result from a low-energy trauma such as a fall from a standing height, i.e., occurring in absence of an adequate trauma. Osteoporotic fractures occur in the following locations: vertebrae, hip, and forearm. These bones have a large proportion of trabecular bone.

What is the WHO criteria for osteoporosis?

Bone density measurements are used to screen women for osteoporosis risk. Reported as T score or Z score, not in absolute units. Z-score is the number of standard deviations above or below the mean for the patient's age, sex, and ethnicity. The diagnosis of osteoporosis is based on a comparison of the patient's bone mass to peak adult bone mass (T score). T-score is the number of standard deviations above or below the mean of peak adult bone mass

How does hypogonadism affect osteoporosis?

Both estrogen and testosterone have major influences on the regulation of bone metabolism. Androgen receptors are present in osteoblasts, where androgens stimulate a variety of osteoblastic functions that are necessary for adequate bone mass development.

Describe the progression of osteoporosis in compact bone.

Changes in cortical bone during osteoporosis occur at a later time. The bone cortex becomes thinner, the medullary canal enlarges. The mechanism of the cortical bone loss consists in the "trabecularization" of the inner cortex. During this process the small pores within the bony cortex, which normally represent Haversian canals and osteocyte lacunae, enlarge progressively until the cortex becomes cancellous-like, and assumes a trabecular structure. After the trabecular connections are progressively lost, the superior and inferior endplates and the cortical rim all attenuate. All these processes result in a severe loss of mechanical competency for individual vertebral bodies.

How do anticonvulsants contribute to osteoporosis?

Chronic anticonvulsant therapy can damage bone over time. This has been confirmed in many epileptic populations worldwide. Patients are found to have osteoporosis, fractures, hypocalcemia, and hypophosphatemia. The mechanisms by which anticonvulsant medication interferes with bone and mineral metabolism remain unclear.

How is trabecular bone distributed in the body?

Each bone consists of an outer portion of cortical, compact bone with a core of cancellous or trabecular bone. Roughly 80% of bone is cortical, and only 20% is cancellous or trabecular. They undergo different rates of remodeling. Compact bone (the cortical bone of long tubular bones) has a very low surface/volume ratio and therefore has a very slow remodeling rate. Only 2.5% of cortical bone is remodeled annually Cancellous bone has a porous structure and a large surface/volume ratio. About 25% of cancellous bone is remodeled annually compared to only 2.5% of cortical bone. It therefore follows that the decrease in bone secondary to exaggerated remodeling is first manifested in bones with a large proportion of trabeculae and therefore with a higher surface area. The proportion of trabecular bone varies with different skeletal regions: (a) lumbar vertebrae 75%; (b) heels 70%; (c) proximal femur 50% - 75%; (d) distal radius 25%; (e) middle of the radius < 5%.

Describe distal radius fractures in osteoporosis patients.

Fractures of the distal radius represent the third most common type of osteoporotic fractures. Distal radius fractures always follow a fall on the outstretched hand. The impact produces a transverse fracture in the distal 2-3 cm of the radius articular surface associated with dorsal displacement of the wrist and hand (Colles fractures).

What is transplantation osteoporosis?

Half of transplant patients eventually develop osteoporosis with fractures, which is due to immunosuppression with corticosteroids, cyclosporin A, and tacrolimus.

Describe osteoporotic hip fractures.

Hip fractures. There are 7 trabecular groups in the proximal femur which indicate pressure or traction according to their orientation. Between them lies an area which is relatively poor in trabeculae called Ward's triangle. As osteoporosis progresses the seven groups of trabeculae are steadily resorbed. Large gaps are produced in the cancellous area (spongiosa): they are located in the Ward's triangle and the great trochanter.

Describe loss of trabecular connectivity

Human trabecular bone is anisotropic with respect to its mechanical properties and architecture. That is to say, the bone does not look or behave identically when held in one position compared to its appearance and behavior following rotation by 90°. Trabecular anisotropy reflects the manner in which gravitational stresses are transmitted through the skeleton. Because human locomotion is bipedal, the upright vertical trabeculae are thicker (approximately 200 micrometers) than horizontal trabeculae. By contrast, arboreal primates show isotropic trabecular bone, i.e. the bone is identical regardless of which side is up. Although horizontal trabeculae are shorter and thinner than vertical trabeculae in humans, they make an important contribution to trabecular strength. The figure below illustrates the difference in ultimate breaking strength (called the Euler buckling load) of supported and unsupported columns of similar dimension. Buckling load is defined as the load at which bending of a structural member subjected to high compressive stress progresses without an increase in the load. In this example, a single horizontal connecting element confers a fourfold increase in load-bearing capacity.

What is juvenile idiopathic osteoporosis?

Juvenile idiopathic osteoporosis (JIO) is a very rare condition of primary bone demineralization. Only approximately 100 cases have been reported in the literature. JIO affects children between 8 and 14 years of age. The exact pathogenesis of this disease is not known. Patients with JIO have very low bone formation rate and fewer remodeling cycles. The major clinical features are pain in the back, hips, and legs with difficulty walking, growth retardation (short stature), dental abnormalities with generalized osteoporosis on x-rays, vertebral compression fractures, and metaphyseal compression fractures of the long bones. Bone mineral density is low with a Z-score of < −2 SD. Laboratory studies are normal.

What are the laboratory studies on patients with osteoporosis?

Levels of serum calcium, phosphate, and alkaline phosphatase are usually normal in persons with primary osteoporosis. The significance of laboratory tests therefore lies mainly in recognizing secondary osteoporosis. Checking the serum levels of thyroxin, cortisol, and parathyroid hormone is prudent because hyperthyroidism, Cushing syndrome, and hyperparathyroidism are frequent causes of secondary osteoporosis.

What is osteoporosis?

Osteoporosis is a metabolic disease of the bone with multifactorial etiology that has a chronic, progressive clinical course. Osteoporosis is characterized by low bone mass, microarchitectural disruption, and skeletal fragility, resulting in decreased bone strength and an increased risk of fracture. In addition, the World Health Organization (WHO) has defined osteoporosis based upon dual-energy x- ray absorptiometry (DEXA) measurements. The relative fracture risk increases as the bone mineral density decreases. The disease often does not become clinically apparent until a fragility fracture occurs.

How do corticosteroids contribute to osteoporosis?

Osteoporosis is nearly always due to long-term therapy with steroid hormones, only rarely to an endogenous Cushing syndrome. Subjects taking corticosteroids have accelerated bone loss which becomes significant as early as 3 months after initiation of therapy. Corticosteroids have a multifaceted effect on bone: inhibit osteoblast and bone formation, stimulate osteoclast and bone resorption, decrease intestinal absorption of calcium, increase renal excretion of calcium.

Epidemiology of osteoporosis

Osteoporosis is the most common metabolic bone disease in the United States. According to the National Osteoporosis Foundation (NOF), 10 million Americans have osteoporosis. Another 34 million have low bone mass (osteopenia), which leaves them at increased risk for osteoporosis. Women are at a significantly higher risk for osteoporosis. According to the NOF, of the estimated 10 million Americans who have osteoporosis, 80% are women. Overall, osteoporosis has a female-to-male ratio of 4:1. The frequency of postmenopausal osteoporosis is highest in women aged 50-70 years. Secondary osteoporosis, however, can occur in persons of any age.

Pathology of osteoporosis

Osteoporosis results from deficits in the amount of normally composed bone. The residual bone is defective in amount and distribution, but not in matrix composition or mineralization Osteoporosis contrasts with osteomalacia: in osteomalacia bone matrix is grossly undermineralized.

What is primary osteoporosis?

Patients are said to have primary osteoporosis when a secondary cause of osteoporosis cannot be identified. Primary osteoporosis can be further subdivided into postmenopausal (type I) and age-associated or senile (type II) osteoporosis. Idiopathic juvenile osteoporosis is also a rare form of primary osteoporosis. Postmenopausal osteoporosis is primarily due to estrogen deficiency. Senile osteoporosis is primarily due to an aging skeleton and calcium deficiency.

How do anticoagulants contribute to osteoporosis?

Patients with operations on cardiac valves and long-term anticoagulant therapy are particularly vulnerable to loss of bone. Heparin stimulates bone resorption and depresses bone formation. Approximately 25% of individuals who are treated with heparin over the duration of 100 weeks, develop osteoporosis and compressive fractures of the spine.

Describe the progression of osteoporosis in cancellous bone

Progression of osteoporosis can be followed in the vertebral bodies. Normal vertebral bodies show vertical trabeculae along the pressure lines and transverse trabeculae along the tension lines. The characteristic changes of osteoporosis first appear in the vertebral center and spread radially. Loss of transverse trabeculae occurs earlier and to a greater extent than vertical trabeculae. Once the trabeculae are lost it is not possible to replace them.

What is hypogonadism caused by radiotherapy and chemotherapy?

Radiotherapy and chemotherapy commonly damage the ovaries and testes: in women, ovarian failure occurs with lack of estrogen production; in men azoospermia develops and serum testosterone level decreases.

What is secondary osteoporosis?

Secondary osteoporosis occurs when an underlying disease, deficiency, or drug causes osteoporosis. Endocrine diseases, immobilization, hypogonadism, and medications are among the most important secondary causes of osteoporosis.

How does immobilization contribute to osteoporosis?

The classical example is the regional osteoporosis which occurs when an extremity is immobilized either because of a fracture or a motor-neuron injury. This bone loss as a consequence of reduction in mechanical loading is often called "disuse osteoporosis". The lack of mechanical strain results in increased osteoclastic resorption. On cessation of immobilization and resumption of activity, the process can be reversed, and the bones normalized.

When do we reach peak bone mass? How is PBM related to osteoporosis?

The skeleton acquires the maximal bone density ('peak bone mass') by the age of 30 years. PBM plays an essential role in the risk of osteoporotic fractures occurring in adulthood. A high PBM reduces osteoporosis risk later in life. It is considered that an increase of PBM by one standard deviation would reduce the fracture risk by 50%.

What is therapeutic hypogonadism?

Therapeutic hypogonadism is an important strategy in controlling hormone-dependent tumors such as most breast and prostate cancers. Estrogen antagonists and inhibitors of aromatase markedly suppress plasma estrogen levels in patients with breast cancer. Patients with prostate cancer receive therapy whose aim is attainment of hypogonadism (orchiectomy, GnRH analogues, and antiandrogens). Estrogen-deficient and androgen-deficient patients are at great risk of developing osteoporosis.

Describe the changes in trabecular structure during osteoporosis development

Thinning of individual trabeculae occurs first. Trabecular plates are transformed into rods by multiple perforations. Loss of the entire trabecular elements leads to loss of trabecular connectivity (disruption of the trabecular architecture). Connectivity is an important feature of skeletal integrity. The negative effect of having fewer, more sparsely placed trabeculae is not counteracted by the increased relative thickness of the residual trabeculae.

How is a DEXA scan performed?

This imaging technique aims two X-ray beams of different intensity at the site of interest. A computer program uses the amount of radiation detected by the scanner to calculate the amount of mineralization at that site.

How does hyperthyroidism affect osteoporosis?

Thyroid hormone excess results in significant bone loss secondary to accelerated bone resorption. Both osteoclast and osteoblast activity are increased but osteoclast activity predominates. Both endogenous hyperthyroidism (Graves' disease) and excessive thyroxine replacement therapy are associated with increased bone loss and fractures.

Is cortical or trabecular bone more affected in type 2 osteoporosis?

Type II osteoporosis occurs in women or men, older than 75 years of age. This type is a process of slow bone loss that primarily affects cortical sites. Fractures associated with type II osteoporosis occur at sites that contain both cancellous and cortical bone, such as femoral neck, vertebral bodies, and long bones (proximal femur, humerus, and tibia). Type II osteoporosis is associated with decreased bone formation and increased bone resorption. Decreased bone formation secondary to a decrease in osteoblast number along with an age-related decreased ability of the kidney to produce calcitriol. Increased bone resorption is a consequence of hyperparathyroidism, mainly due to a lack of calcitriol.

What can imaging show you when diagnosing osteoporosis?

X-rays are not appropriate for early diagnosis. Skeletal radiographs indicate bone loss only when the density has been reduced by 30-40%. But skeletal radiographs are very useful to detect the complications of osteoporosis i.e. to reveal previous fractures or compressions.