Understanding Osteoporosis, Case Study Example

What is the effect of age, race and gender on bone density?

In general, bone density decreases with increasing age (>65), Caucasian ethnicity and female gender due to differences in estrogen profiles. This phenomenon can be understood as a result of differing estrogen profiles linked to menopause, ethnic variability in relation to bone density and Vitamin D synthesis and gender. It is critical that all patients within this high risk profile are aware of therapy options.

Define DEXA

Dual-emission X-ray absorptiometry is a technique designed to measure bone mineral density. DEXA works by firing two X-ray beams with differing energy levels directly at the patient’s bones. When non-bone absorption is subtracted, the BMD can be defined. DEXA is one of the most widely used bone density measurement technologies.

Define T-score

This is a common measure for osteoporosis screening. It takes the BMD of the patient and compares it with a reference normal 30-year old same sex mean. The criteria is Normal (-1 Standard Deviations or more), Osteopenia (-1 to -2.5) and Osteoporosis (-2.5 or less). However, it is important to stress that clinical judgment is important to diagnosis in less studied populations such as non-post-menopausal women, endocrine abnormal patients and men.

Define Z-score

A z-score is the numerical comparison for the patient to an aged-matched normal reference. It is more specific than T-score and is used for unusual T-score patients such as in pre-menopausal women, young men and children and can be used to detect co-existing illnesses such as parathyroid disease or abnormal endogenous/exogenous steroid levels.

Explain the difference between osteopenia and osteoporosis per the World Health Organization definition

Osteopenia is considered a major risk factor for the development of osteoporosis. The quantitative diagnostic difference between osteopenia and osteoporosis is the measure of bone mineral density as defined by a patient’s t-score. However, the condition can be understood as a more severe manifestation of the same phenomenon.

Can you identify any data from Ms Gs history thus far that might put her at risk for osteopenia or osteoporosis?

Risk factors are age, gender, post-menopausal state, endocrine history, activity level and a history of fractures are the non-modifiable factors in osteoporosis. Patients must be made aware of these conditions though modifiable changes should be stressed.

List the modifiable and non-modifiable risks for osteoporotic fractures

The non-modifiable factors are age, ethnicity, gender and endocrine history. Modifiable factors are activity level (i.e. resistance weight training), high-calcium vitamin supplementation and proper nutrition with dairy products.

Name supplements and nonpharmacologic means of preventing osteoporosis

Supplemental means are Calcium, Vitamin D, bisphosphanates and estrogens. Non-pharmaceutical means are strength training, proper nutrition, and avoidance of falls, alcohol and tobacco.

What is the relationship of vitamin D to calcium? or explain the physiology of calcium and vitamin D; Why is vitamin D important to bone health?

Vitamin D is involved in the absorption of calcium in the intestines. In Vitamin D’s absence, rickets can develop. The hallmark of osteoporosis is a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Under physiologic conditions, bone formation and resorption are in a fair balance. A change in either—that is, increased bone resorption or decreased bone formation—may result in osteoporosis. Osteoporosis can be caused both by a failure to build bone and reach peak bone mass as a young adult and by bone loss later in life. Accelerated bone loss can occur in perimenopausal women and elderly men and women and can occur secondary to various disease states and medications.

Loss of gonadal function and aging are the 2 most important factors contributing to the development of osteoporosis. Studies have shown that bone loss in women accelerates rapidly in the first years after menopause. The lack of gonadal hormones is thought to up-regulate osteoclast progenitor cells.

What are recommended daily requirements for vitamin D and calcium per the 2010 Institute of Medicine (IOM) report?

The recommended daily requirements for Calcium is 1000IU and Vitamin D is 400IU for a patient in Ms G’s age profile.

What is the mechanism of action of the biphosphonates?

The mechanism of action of bisphosphanates is that they have a significant similarity to pyrophosphates. Therefore, the bisphosphanate group is similar to the pyrophosphate structure which allows it to inhibit the action of the enzymes which break down bone.

What patient teaching must accompany the use of biphosphonates?

It is important that patients understand that bisphosphanates may upset the GI track leading to erosions of the esophagus when taken orally. It is important that patients remain seated for an hour after ingestion. In general, patients should be educated about the risk factors for osteoporosis, with a special emphasis on family history and the effects of menopause. Patients also need to be educated about the benefits of calcium and vitamin D supplements. All postmenopausal women should be offered bone densitometry, and they should understand the benefits of bone density monitoring.

What do these scores mean?

Her t- score suggests she has osteoporosis. This is a common measure for osteoporosis screening. It takes the BMD of the patient and compares it with a reference normal 30-year old same sex mean. The criteria is Normal (-1 Standard Deviations or more), Osteopenia (-1 to -2.5) and Osteoporosis (-2.5 or less). However, it is important to stress that clinical judgment is important to diagnosis in less studied populations such as non-post-menopausal women, endocrine abnormal patients and men.

What is your choice for therapy for Ms G?Why?

As the patient is 65, female and has a history of endocrine abnormalities and falls, I would act aggressively and prescribe bisphospanates along with lifestyle modification. The differential diagnosis of osteoporosis to be considered includes all the secondary causes. When dealing with reduced bone density, other possible causes of symptoms must be eliminated before treating the patient for osteoporosis. Many patients have a coexisting cause of bone loss.

The differential diagnosis of an atraumatic compression fracture may include osteomalacia, tumor, osteonecrosis, infection, and other bone-softening metabolic disorders. Metastatic bone disease should always be ruled out when one is treating multiple fractures. Osteoporosis may be confused with osteomalacia, but in osteoporosis, the bones are porous and brittle, while in osteomalacia the bones are soft. This difference in bone consistency is related to the mineral-to-organic material ratio. In osteoporosis, the mineral-to-collagen ratio is within the reference range, whereas in osteomalacia, the proportion of mineral composition is reduced relative to organic mineral content.

The presence of a fracture often is not only a marker for decreased bone mass but also potentially a symptom of failing health in general and 1 or more primary disorders in particular. Failure to diagnose and/or make appropriate referrals may create potential legal issues. Other conditions to be considered include the following: Homocystinuria, Leukemia, Lymphoma, Mastocytosis, Metastases (bony and other), Pathologic fractures secondary to bone metastases from cancer, Pediatric osteogenesis imperfect, Renal osteodystrophy, Scurvy, Sickle cell anemia

She is started on your chosen therapy and she is to have a follow up bone density in how many months?

Two years is the recommended length between DEXA measurement.

What do you think could be a cause of her dysphagia?

It is likely that her dysphagia is a result of esophageal inflammation/erosion due to bisphosphantes.

What is the recommended length of biphosphonate therapy and why?

The recommended length is less than 5 years as numerous studies have found a 10% increase in esophageal cancer after this amount of time due to constant inflammation.

List antiresorptive drugs and bone forming therapy that would be treatment choices for Ms G following biphosphonate use.

After bisphospanate therapy, Ms. G could take SERMs like Raloxifene or recombinant parathyroid analogs such as Forteo. In addtition, nutritional supplementation should be encouraged.

References

Bono CM, Einhorn TA. Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J. Oct 2003;12 Suppl 2:S90-6

Brian K Alldredge; Koda-Kimble, Mary Anne; Young, Lloyd Y.; Wayne A Kradjan; B. Joseph Guglielmo (2009). Applied therapeutics: the clinical use of drugs. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 101–3

Fleisch H (2002). “Development of bisphosphonates”. Breast Cancer Res 4 (1): 30–4.