Osteoporosis Workup and Treatment

Osteoporosis workup and treatment is a common procedure in family and internal medicine. This disease is one of the most common bone diseases in the United States. Osteoporosis is a skeletal bone disease, and characterized by low bone mass. This conditions is the result of deterioration of the bone tissue with an increase in fragility and higher risk of fracture. Sadly, there are no signs and symptoms of osteoporosis until a patient has a fracture. Therefore, screening is critical to help prevent fractures in at-risk patients with the disease.

Screening Guidelines

Bone density peaks around 30 years of age. After that age, bone loss begins. As we age, we can expect our bone density to go down. The United States Preventive Services Task Force (USPSTF) Recommends screening for women over 65 and women younger than 65 at an increased risk of osteoporosis. Risk factors include excess alcohol consumption, parental history of hip fracture, smoking, and low body weight. These risk factors help to identify the need for osteoporosis workup and treatment.

DEXA Scanning

Central dual-energy x-ray absorptiometry (DEXA) screening is the standard test to diagnose osteoporosis. DEXA measures bone mineral density (BMD). This is what most guidelines will use for parameters for treatment. The DEXA scan compares the patient’s bone density with normal expected bone density for people of similar age. Normally, the trabeculae of normal bone provides a structural support for the bone.

As we age, we produce fewer bone cells. Likewise, the trabecular meshwork of bone structure weakens. The concept of DEXA scanning is straightforward. DEXA sends two X-ray beams at different peak energy frequencies to the target bones. Both bones and soft tissue absorb X-ray beams. The amount of absorption varies by bone density. Likewise, the amount of soft tissue absorption also varies. The difference between total absorption and soft tissue absorption is the bone mineral density (BMD). The patient’s BMD is then compared to average age values. Below average results are assigned a T score. The patient’s T-score defines both low bone density and Osteoporosis. This is the crucial value needed to complete osteoporosis workup and guide treatment.

Making the Diagnosis

Osteoporosis is diagnosed when the T-score is less than 2.5 standard deviations (SD) below the mean for age. The World Health Organization defines normal as a T-score within 1 SD of the mean BMD in a healthy young adult. T-scores of -1 to -2.5 standard deviation indicate osteopenia (between normal and osteoporosis). Screening should be repeated every two years. A low density score does not necessarily predict an increased risk of fracture. Therefore, it is helpful to identify a loss of bone density, but its clinical utility for fracture prediction is not reliable.

The Sheffield Frax tool is a reliable tool for fracture prediction. Note that this estimate also requires the bone mineral density (BMD) of the femoral neck. The DEXA report includes this value. Common locations for density comparison include the The femoral neck and lumbar spine. You can find these density values on the DEXA scan results.

Treatment

Once you have completed the osteoporosis workup, treatment needs to be determined. Women whose bone density test shows T-scores of -2.5 or lower, such as -3.3 or -3.8, should begin therapy to reduce their risk of fracture. Many women need treatment if they have osteopenia, which is bone weakness that is not as severe as osteoporosis. The treatment for osteoporosis should include supplementation with vitamin D and calcium, lifestyle modification to improve skeletal health (increase weight bearing and muscle strength training), and prescription medications.

Bisphosphonates

The class of medications most commonly used for osteoporosis are bisphosphonates. Alendronate is currently approved for the treatment of osteoporosis. These medications are effective for both the prevention and treatment of osteoporosis. These drugs increase bone mass and reduce the incidence of fractures.

Oral bisphosphonates should not avoided in patients with certain conditions. There include esophageal disorders, an inability to follow the dosing requirements (eg, stay upright for at least 30 to 60 minutes), or chronic kidney disease (CKD; estimated glomerular filtration rate <30 mL/min). Oral bisphosphonates should also be avoided after certain types of bariatric surgery in which surgical anastomoses are present in the gastrointestinal tract (eg, Roux-en-Y gastric bypass).

Hormonal, Antiresorptive, and Anabolic Therapy

Patients with severe osteoporosis (eg, T-score of ≤-3.0 even in the absence of fractures, T-score of ≤-2.5 plus a fragility fracture, severe or multiple vertebral fractures) may benefit from initial treatment with an anabolic agent such as teriparatide, abaloparatide, or romosozumab). The cost of anabolic therapy, subcutaneous route of administration, and long-term safety concerns may restrict patient compliance.

In a double-blind, double-placebo controlled trial comparing teriparatide with risedronate in 680 postmenopausal women (mean age 72.1 years) with severe osteoporosis (mean number of prevalent fractures 2.7), there were fewer new radiographic vertebral fractures in the teriparatide group (5.4 versus 12 percent) and fewer clinical fractures at all sites (4.8 versus 9.8 percent). There was no difference in the incidences of nonvertebral fractures. The majority of women had received at least one previous osteoporosis medication (median duration of previous bisphosphonate use 3.6 years).

Denosumab

Denosumab is not the recommended initial therapy for most patients with osteoporosis. However it can be used initially in certain patients. This includes patients at high risk for fracture, such as older patients who have difficulty with the dosing requirements of oral bisphosphonates or who have markedly impaired renal function. In addition, denosumab is an option for patients who are intolerant of or unresponsive to other therapies (including IV bisphosphonates) and in those with impaired renal function.

However, emerging data have raised concern about increased risk of vertebral fracture after discontinuation of denosumab. Patients who have stopped taking denosumab should be started on Bisphosphonates. This helps to prevent rapid bone loss and vertebral fracture.

Selective Estrogen Receptor Modulators – Raloxifene

Raloxifene inhibits bone resorption and reduces the risk of vertebral fracture, and it is our SERM of choice because it has eight-year safety and efficacy data and also reduces the risk of breast cancer. Raloxifene can be chosen for osteoporosis when there is also a need for breast cancer prophylaxis.

Estrogen

Estrogen-progestin therapy is no longer a first-line approach for the treatment of osteoporosis in postmenopausal women, because of increased risk of breast cancer, stroke, venous thromboembolism (VTE), and perhaps coronary disease (although the risk-benefit profile in the unopposed estrogen trial was different). Indications for estrogen-progestin therapy in postmenopausal women include persistent menopausal symptoms and women with an indication for antiresorptive therapy who cannot tolerate the other drugs.

Anabolic Agents

In contrast to antiresorptive agents, anabolic agents stimulate bone formation and activate bone remodeling. The anabolic agents teriparatide and abaloparatide are not initial therapy for most patients. Candidates for anabolic agents include men or postmenopausal women with severe osteoporosis (T-score of ≤-3.5 even in the absence of fractures, or T-score of ≤-2.5 plus a fragility fracture), patients with osteoporosis who are unable to tolerate bisphosphonates or who have contraindications to oral bisphosphonates (achalasia, scleroderma involving the esophagus, esophageal strictures), and patients who fail other osteoporosis therapies (fracture with loss of BMD in spite of compliance with therapy).

Romosozumab

Romosozumab is a monoclonal anti-sclerostin antibody. Sclerostin is produced by osteocytes and inhibits bone formation. This agent is not considered initial therapy for most patients with osteoporosis. Possible candidates include patients at with multiple fragility fractures, those at high risk for fracture who cannot tolerate any other osteoporosis therapies, or those who fail other osteoporosis therapies (fracture with loss of BMD in spite of compliance with therapy). Data for this medication is also based on limited clinical trials. The drug’s side effect profile is still being investigated.

Calcium Supplementation

Patients should take lifestyle measures to reduce bone loss. These measures include adequate calcium and vitamin D, exercise, smoking cessation, counseling on fall prevention, and avoidance of heavy alcohol use. In general, we recommend 1200 mg of elemental calcium daily. This total Includes both dietary and supplemental calcium. In addition, we suggest 800 international units of vitamin D daily. Postmenopausal women who are getting adequate calcium from dietary intake alone do not need to take calcium supplements

Monitoring Treatment

Monitoring the response to therapy is important for identifying patients who may require a change in therapy. Up to one-sixth of women taking alendronate continue to lose bone. There are several published guidelines for monitoring the response to osteoporosis therapy; all recommend follow-up BMD (DEXA) testing.Despite the need for monitoring, there is no consensus on the optimal approach.

Osteoporosis workup and treatment can be considered a lifetime process. Serial DEXA measurements are typically used to assess the BMD response. However, most of the efficacy of bisphosphonates in fracture reduction is not captured by DEXA. We suggest a follow-up DEXA of hip and spine after two years, and if BMD is stable or improved, less frequent monitoring thereafter.

Summary

Osteoporosis and decreased bone density are common conditions that we should expect as we age. This is more common in females, and routine testing helps to identify both the risk of fracture and the need for treatment. Providers working in the outpatient and even acute care setting should consider these conditions relative to their management and treatment options.

Lancet. 2018 Jan 20;391(10117):230-240. doi: 10.1016/S0140-6736(17)32137-2. Epub 2017 Nov 9. [PUBMED]

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