Does this patient have glucocorticoid-induced osteoporosis?

  • Glucocorticoids (GCs) have many side effects. One of the most devastating can be osteoporosis and fracture. Although no dose of glucocorticoid is considered entirely safe for bone, the higher the dose of glucocorticoid, the greater the effect on bone. The effect is also most prominent during the first 3-6 months on glucocorticoids, when a rapid loss of bone mineral density is noted. The loss is slower thereafter. Studies have shown an increased risk of fracture in patients with both a prior history of GC use as well as current use of GCs.

  • Glucocorticoids directly inhibit osteoblasts and increase osteocyte apoptosis. Glucocorticoids increase osteoclast survival and increase bone resorption. In addition, glucocorticoids decrease intestinal calcium absorption and increase urinary calcium excretion. This results in secondary hyperparathyroidism and increased bone resorption. GCs can also inhibit gonadotropin secretion causing hypogonadism, which has a detrimental effect on bone.

  • Osteoporosis is a silent disease. The first sign of osteoporosis in a patient on GCs is often a vertebral fracture. Height loss of more than 2 inches may correlate with a vertebral fracture. Thoracic kyphosis may also be the result of a vertebral fracture.

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What tests to perform?

  • A Dual-Energy X-ray Absorptiometry (DEXA) should be considered in patients receiving frequent courses of GCs or in patients expected to be on GCs for a prolonged period of time. The American College of Rheumatology (ACR) recommends a DEXA in adults with risk factors for osteoporosis. Many would argue that in all patients being placed on GCs, a DEXA should be obtained if the patient has not had one within the past 1-2 years. It is also prudent to obtain a Vertebral Fracture Assessment (VFA) at the time of the DEXA. This would allow diagnosis of any prevalent vertebral fractures. The National Osteoporosis Foundation (NOF) recommends obtaining a DEXA if a patient is on prednisone or an equivalent of 5 mg/day or greater for 3 or more months.

  • It is reasonable to obtain a 25-OH vitamin D level and an intact parathyroid hormone level (with a serum calcium), especially since GCs can cause secondary hyperparathyroidism. Bone resorption can be assessed with a serum CTX or a urine NTX. Bone formation can be assessed with a measurement of osteocalcin or bone alkaline phosphatase. If other causes of osteoporosis are suspected, additional testing may be warranted. Examples include: celiac screen, SIEP, UIEP, ESR, TSH, phosphorus, homocysteine, urine calcium.

  • Bone biopsies are rarely needed in glucocorticoid-induced osteoporosis (GIO). Biopsies reveal more rapid loss of trabecular bone, as opposed to cortical bone.

  • The DEXA should be used to assess whether the patient has normal bone density, osteopenia or osteoporosis. The lowest T-score (i.e., spine, femoral neck, total hip or forearm) determines the diagnosis. The Bone Mass Act of 1998 permits yearly DEXA scan in patients on GCs. If a patient has a vertebral fracture by vertebral fracture assessment (VFA), the diagnosis of osteoporosis is made regardless of the T-score.

  • Degenerative disease in the spine and occasionally in the hip can falsely elevate the DEXA reading. A quantitative CT of the spine can more precisely diagnosis osteoporosis in these patients.

How should patients with steroid-induced osteoporosis be managed?

  • The ACR had guidelines for the prevention and treatment of GIO was recently published. A clinical fracture risk assessment should be done annually. For adults with osteoporosis, an elevated FRAX, on a dose of GC ≥ 30 mg/day or significant risk factors for osteoporosis, treatment is recommended.

  • The initial treatment for consideration is oral bisphosphonates. Second line therapy is teriparitide. When these drugs are not appropriate IV bisphosphonate and denosumab can be considered. Lastly, raloxifene can be considered in postmenopausal women.

  • In a study comparing alendronate to teriparatide in GIO, teriparatide demonstrated a significant increase in lumbar bone mineral density (BMD) by 6 months and a significant increase in hip BMD by 12 months. Fewer new vertebral fractures occurred in the teriparatide group. For this reason, patients on GCs with lower BMD or with multiple risk factors for osteoporosis may benefit more from teriparatide than from bisphosphonate therapy. The ACR Guidelines took cost and ease of administration of oral bisphosphonates into consideration and that is why teriparatide was not considered a first line agent in GIO.

  • All patients should be counseled to avoid tobacco, excess alcohol and caffeine and to get appropriate calcium and vitamin D.

  • All patients should be instructed to participate in a regular weight-bearing exercise program. A falls assessment should be made in patients at risk for falls. The home environment should be evaluated and whenever possible, actions taken to reduce the risk of falls in the home.

  • Excess salt has been associated with osteoporosis and patients should be instructed to limit their salt intake.

  • The treating physician should always aim to use the lowest dose of GC and to treat for the shortest duration possible.

  • A DEXA should be obtained yearly in patients on GCs.

What happens to patients with steroid-induced osteoporosis?

If GCs are discontinued thought can be given to discontinuation of pharmacologic therapy. The urine NTX can be helpful in assessing whether therapy can be held. If the urine NTX is less than 20 nM BCE (bone collagen equivalent) per 1 mM creatinine, bisphosphonates can be held and the patient followed with a DEXA scan periodically. If the patient has osteoporosis, treatment decisions should be reassessed annually.

How to utilize team care?

  • For patients with severe osteoporosis requiring GCs or for patients in whom the DEXA is declining despite seemingly appropriate therapy, consultation with a physician who specializes in bone health is indicated. Many endocrinologists and some rheumatologists specialize in bone health.

  • Nurse Practioners can help run programs to care for patients with osteoporosis or with osteopenia and risk factors for fracture. Often the bone health of patients on GCs is not addressed. Having a service that can evaluate and treat these patients would hopefully increase the rate of treatment of these patients.

  • If there is a concern about low calcium and vitamin D intake, the patient can be sent to a dietitian. The dietitian can suggest intake of foods high in calcium and vitamin D. If the intake is not sufficient, supplements can be suggested. In patients with a history of calcium oxalate kidney stones, calcium citrate supplementation will not increase the risk of stones and may well aide in decreasing the rate of stone recurrence. The National Osteoporosis Foundation (NOF) recommends at least 1200 calcium/day and at least 1000IU vitamin D/day.

  • Patients should be instructed on a proper weight-bearing exercise program. It is often helpful to send the patient for physical therapy. The physical therapist can design a home program that would be safe and beneficial to improve balance and muscle strength.

Are there clinical practice guidelines to inform decision making?

  • The American College of Rheumatology updated their Recommendation for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis in 2017.

  • Patients on GCs should be evaluated individually and an appropriate treatment plan designed.

Other considerations

GIO M81.8