Does the patient have osteoporosis?

Osteoporosis is defined by bone mineral density (BMD). Testing is best done with dual-energy x-ray absorptiometry (DEXA). The T-score compares the patient to a healthy gender and ethnicity-matched 30 year old. This age is used for comparison because it correlates with peak bone mass.

If the T-score is -2.5 SD or lower, osteoporosis is diagnosed. If the patient has had prior osteoporotic fractures, the patient is felt to have severe osteoporosis. A low impact fracture is considered an osteoporotic fracture. This would include a fracture sustained from a standing position or a fracture sustained after low trauma, i.e. a vertebral fracture after raking leaves. Osteoporosis is a systemic skeletal disorder that is associated with an increased fracture risk.

What tests to perform?


The gold standard imaging study for the evaluation of osteoporosis is the DEXA scan. The DEXA scan measures density in gm/cm3 and relates that to a T-score and Z-score. The T-score compares the density to a gender and ethnicity-matched 30 year old healthy control. The Z-score compares the density to age-matched controls.

The U.S. Preventative Task Force recommends a baseline BMD in women at age 65 or younger if there are risk factors for osteoporosis. The NOF recommends a baseline BMD for women at menopause and for men at age 70.

A DEXA can be repeated every 1-3 years. If a patient has a decreased BMD and risk factors for rapid bone loss, the BMD should be done annually. Examples would include a perimenopausal state, use of glucocorticoids, use of aromatase inhibitors, or a state of malabsorption.

Whenever possible, the patient should repeat the DEXA at the same location. Comparison is best done in this way. Data from different types of DEXA machines, i.e. Hologic and Lunar, cannot be easily compared. Quantitative CT may prove more accurate in defining microarchitecture of bone. To date, peripheral ultrasound measurements are not felt to be as accurate as DEXA.

Laboratory testing

If the patient has osteoporosis, it is reasonable to collect baseline lab tests. These would include 25-vitamin D and intact PTH/serum calcium levels. This helps to assess if the patient is getting enough calcium and vitamin D. Secondary hyperparathyroidism should be corrected, as it is associated with skeletal calcium loss. Most in the field agree that if a patient has osteoporosis, the 25-vitamin D level should be maintained at 32-50ng/ml.

A urine N-telopeptide (NTX) or a serum C-telopeptide (CTX) can help assess the rate of bone resorption. Osteocalcin or bone alkaline phosphatase can help assess bone formation rates. If the patient has a Z-score more than 1 SD below age-matched controls, or if the BMD is declining, despite seemingly appropriate therapy, additional testing should be done.

Based on the clinical scenario, additional testing may include: evaluation for celiac disease, multiple myeloma, undiagnosed inflammatory states, phosphorus, cortisol, homocysteine and urine calcium.

In general, a metabolic evaluation is done yearly. If the patient is felt to be lacking in calcium and/or 25-vitamin D, repeat testing on supplementation should be repeated in 8-12 weeks.

Vertebral fracture assessment

A vertebral fracture assessment (VFA) can be done at the time of the DEXA. The VFA can detect prior vertebral fractures. The history of a prior, undiagnosed fracture will aide in decisions regarding therapy. Only half of all vertebral fractures are symptomatic.


Bone Biopsy is rarely necessary. Often with laboratory testing, rates of bone formation and bone resorption can be ascertained. Laboratory testing can help to evaluate for cause of osteomalacia. There are specific instances when a bone biopsy may be helpful.

If a patient has had a vertebral fracture, a biopsy may help to exclude malignancy. In patients with renal failure, a bone biopsy would help to assess more precisely the rates of bone formation and resorption.

An international organization, Kidney Disease Improving Global Outcomes (KDIGO), has issued guidelines to help care for bone health in patients with chronic kidney disease. If an antiresorptive therapy is being considered in a patient with chronic kidney disease stages 4-5, a bone biopsy can help to exclude adynamic bone disease.


Patients with osteoporosis are at high risk for fracture. The DEXA scan can help define who has osteoporosis. Laboratory testing can help diagnose states of low calcium and vitamin D steady state and help exclude causes of osteomalacia. By defining rates of bone formation and resorption, a more accurate treatment plan can be designed.


The DEXA test has its limitations. Each site is supposed to calculate precision studies to determine if a given change is statistically significant. In general a change must be over 3% to be considered statistically significant. Degenerative disease can falsely elevate the spine BMD. Having had a total hip replacement or repair of a hip fracture with hardware makes this site obsolete for interpretation.

There is also controversy on the on the use of bone markers. The spot urine NTX should be a fasting, second-voided urine. Blood in the urine can affect the results. Some feel there is variability in the results and the test lacks sensitivity and specificity. The serum CTX may be more reliable than the urine NTX.

How should patients with osteoporosis be managed?

Patients with osteoporosis should have a DEXA every 1-2 years. Medicare reimburses for a DEXA every 2 years unless the patient is on corticosteroids or has primary hyperparathyroidism, when DEXA is covered yearly. Commercial insurance plans have their own guidelines, but generally cover DEXA scans every 1-2 years.

Patients should be questioned about any new medical conditions or medications that may affect bone health. They should be questioned about balance and recent falls. For patients on bisphosphonates, patients should be questioned about active dental issues as a screen for osteonecrosis of the jaw and for thigh pain as a screen for an impending stress fracture of the femur.

On a yearly basis, laboratory testing can be done to ensure that the patient is receiving an adequate amount of calcium and vitamin D. This is best done with an intact PTH/serum calcium and 25 vitamin D level. Bone resorption can be measured with a urine NTX or serum CTX.

What happens to patients with osteoporosis?

We all reach peak bone mass at age 30. For men and women there is a slow steady decline in BMD as we age (0.5-1%/year), even if we exercise and get sufficient calcium and vitamin D. For women, in the 1-2 years before menopause and for up to 5 years after menopause, there can be a loss of BMD of 2-5 %/year. If a patient has osteoporosis and is untreated, we will expect a decline in BMD.

Each year in the U.S., there are approximately 300,000 hip fractures, 600,000 vertebral fractures and 400,000 wrist fractures. One in two women and one in five men will suffer an osteoporotic fracture during their lifetime.

The economic burden to society is great. There are the actual health costs associated with treatment of the fracture, but also the costs associated with the impact to the patient or family members on the work force.

The risk of mortality after hip fracture is 10-20%; it is higher for men than for woman. Multiple vertebral fractures and subsequent thoracic kyphosis can be associated with poor body image, dyspnea and early satiety.

As bone resorption outpaces bone formation after the age of 30, there is an overall decrease in BMD. Trabeculae thin and eventually can become disconnected. This weakens the overall structure of the bone.

There is also evidence that in rapid states of bone loss, bone appears to be weaker. This is obvious in glucocorticoid induced osteoporosis. For the first 3 months of glucocorticoid use, especially in high dose use, there is rapid bone loss and an increase in fracture risk. For these reasons, treatment of patients with osteoporosis is critical.

All patients with osteoporosis should be instructed on the proper intake of calcium and vitamin D. If a patient is receiving enough from diet, additional supplementation is not necessary. The National Osteoporosis Foundation (NOF) has a calcium and vitamin D calculator on its website.

All patients should be instructed on a proper weight-bearing exercise regimen. For patients with osteoporosis of the spine, trunk flexion exercises should be avoided, as this can increase the risk of vertebral fractures. High impact sports, like running, may also increase the risk of fractures. Swimming, although a good exercise for cardiovascular health, is not a weight-bearing activity.

Patients should be instructed on falls prevention. Nursing services can often go to a patient’s home and make suggestions to make the home safer.

Patients should be instructed to avoid tobacco and limit alcohol. Both tobacco and excess alcohol are toxic to the osteoblast.

The NOF recommends treating patients 50 years or older who have had a hip or vertebral fracture or with a T-score <=-2.5 with an FDA-approved medication for the treatment of osteoporosis.

Pharmacologic therapy

Pharmacologic therapy should be divided into two categories: anti-resorptive and anabolic therapy.

Anti-resorptive therapy

Anti-resorptive FDA-approved treatment for osteoporosis includes hormone replacement therapy, bisphosphonate therapy, denosumab, raloxifene and calcitonin. The only FDA-approved anabolic agent is teriparatide.

Raloxifene reduces the risk of vertebral, but not hip fractures. Its use is not appropriate for a patient with hip osteoporosis. It can increase the risk of hot flashes, leg cramps and thrombosis.

Calcitonin is a very weak antiresorptive agent and does not have a significant role in the treatment of osteoporosis; there is anecdotal evidence that it may reduce the pain associated with a new fracture.

Bisphosphonates reduce the risk of hip and vertebral fractures. The number of hip fractures has decreased in the world, since the use of alendronate. Studies with risedronate have shown fracture reduction within 6 months of use.

The agents available orally include:

  • Alendronate 10 mg daily and 70 mg weekly.

  • Risedronate 5 mg daily, 35 mg weekly, 75 mg on 2 days monthly and 150 mg monthly

  • Ibandronate 150 mg monthly.

Alendronate and Risedronate are available in generic forms. Alendronate and risedronate should be taken on an empty stomach with 6-8 ounces of water; patients should wait 30 minutes before eating and remain upright for 30 minutes. It is recommended to wait 60 minutes before eating with ibandronate. Ibandronate is also available as a 3mg intravenous push (IVP) preparation dosed every 3 months.

Zoledronic acid is prescribed intravenously 5 mg yearly. Zoledronic acid has been shown to reduce the risk of mortality and reduce the risk of subsequent osteoporotic fractures when given within 90 days after repair of a low-trauma hip fracture. The precise reason for this has not been fully elucidated.

Adverse events associated with bisphosphonates

Oral bisphosphonates can cause esophagitis and less frequently, gastritis and lower gastrointestinal irritation. The overall risk is small. A head-to-head study with alendronate and risedronate demonstrated a statistically significant lower risk of esophagitis with risedronate.

There are case reports of patients developing esophageal cancer while on bisphosphonates; it is recommended that patients with a history of Barrett’s esophagitis be prescribed a parenteral bisphosphonate such as ibandronate or zoledronic acid. Prescribers should question patients on bisphosphonates for reflux-like symptoms.

There is a very small risk of osteonecrosis of the jaw (ONJ) in patients on bisphosphonates. The risk seems to be greater in patients on higher dose therapy, i.e. monthly zoledronic acid for metastatic disease in patients with diabetes, in patients on glucocorticoids and in patients with poor dental hygiene. The American Dental Association (ADA) estimates the highest reliable estimate of ONJ in patients on bisphosphonates is 0.10 %.

The ADA has a position statement that recommends dental work be completed when necessary regardless of prior bisphosphonate use. Patients on bisphosphonate therapy should be instructed to get regular dental care. Both the ADA and the NOF acknowledge that in patients with osteoporosis, the use of bisphosphonates outweighs the risks; patients on bisphosphonate therapy should be monitored on a regular basis.

There is also a small risk of atypical fractures of the femur, in patients on bisphosphonate therapy. Patients often note thigh pain prior to the fracture and some feel as if the fracture occurred and then they fell. Patients on bisphosphonates should be instructed to tell their health care providers about thigh pain and x-rays should be obtained in patients on bisphosphonates with thigh pain. The appearance of the x-ray is fairly typical with stress reaction seen early on and a classic “beaked” appearance on x-ray in patients with this type of fracture.

The concept of a low bone turnover state may explain some of the adverse effects associated with bisphosphonate use. If bone resorption is markedly decreased, it may be difficult to repair microdamage in bone. Many in the field favor a “holiday” off bisphosphonate therapy after 5 years of use. Alternatively, a urine NTX can be done yearly. If the NTX is <20, a “holiday” can be recommended. For patients with osteoporosis on a “holiday”, an NTX can be done yearly; if the NTX rises above 30, consideration for restarting therapy is indicated.


Denosumab is a human anti-RANL ligand antibody. It is FDA-approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture, male osteoporosis and cancer-induced bone loss. It is a subcutaneous injection once every 6 months.

Side effects are similar to the side effects seen with bisphosphonates, but there is no GI irritation.

Anabolic Therapy

Teriparatide is FDA approved for postmenopausal osteoporosis, glucocorticoid induced osteoporosis and male associated osteoporosis. It is an anabolic agent (anabolic agents promote bone formation by the osteoblast). It reduces the risk of both vertebral and nonvertebral fractures. It is a daily self-injectable medication; the pen doses 20 mcg/injection. The pen lasts 28 days and can be out of the refrigerator for 24 hours/month. The needle is a 31 gauge needle and for most patients is associated with minimal pain and uncommon site reactions.

Teriparatide has a “black-box warning” as there was an increased incidence of osteosarcoma in rats, but not in dogs, monkeys or humans who received teriparatide. There is a small incidence of hypercalcemia in patients on teriparatide. In a practical sense, if a patient develops hypercalcemia on teriparatide, the patient can decrease or discontinue oral calcium supplementation and the serum calcium level can be repeated.

It is rare that teriparatide has to be discontinued for hypercalcemia. It can rarely be associated with orthostatic hypotension, usually for the first several days. This can generally be avoided by asking patients to begin it at night and to sit for 30 minutes after the injection.

Teriparatide is indicated in patients with severe osteoporosis, patients on antiresorptive therapy with a declining BMD, patients with a new fracture on antiresorptive therapy and patients on glucocorticoids felt to be at high risk for osteoporotic fracture.


Abaloparatide was recently FDA approved for postmenopausal women at high risk for fracture. It is an anabolic agent. It reduces the risk of both vertebral and nonvertebral fractures. It is a daily self-injectable medication; the pen doses 80 mcg/ dose. It does not have to be refrigerated. It also has the warning to avoid in patients at risk for osteosarcoma. The rate of hypercalcemia is lower than with teriparatide.

How to utilize team care?

Specialty consultations

For patients with difficult to treat osteoporosis, a consultation can be obtained with a physician who specialized in osteoporosis. This is often an endocrinologist or a rheumatologist.


Nurse Practitioners can be valuable in helping to treat patients in Osteoporosis Centers.


Patients should be instructed to discuss any new medications with their pharmacist to ensure all medications are compatible.


If patients seem not to be getting enough calcium and/or vitamin D, a nutritionist can help a patient maximize intake through diet and if needed, add supplements of calcium and vitamin D.


Physical therapists can devise weight-bearing exercise programs that patients can continue to do at home. For patients with poor balance, exercises for balance training are essential.

Are there clinical practice guidelines to inform decision making?

The American Society of Bone and Mineral Research (ASBMR) has a position statement on the use of calcium in the treatment of osteoporosis. The ASBMR does not feel current evidence supports the concept that oral calcium intake increase the risk of vascular calcification.

The American Dental Association (ADA) has a position statement that prior use of a bisphosphonate should not preclude any necessary dental work.

Other considerations

ICD- codes

  • M81.0

The media very often focuses on the rare side effects of pharmacologic therapy and not on the risk of fracture in a patient with low bone density. Patients should be instructed to have their bone health evaluated yearly and treatment adjusted according to changes in health status. Patients may be able to take holidays off medication, but close follow-up with their physicians is necessary.