Glucocorticoids Alter Bone Care Dramatically

DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.

“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”

Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra. “This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids, said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis.

Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”

Patient No. 1

A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.

As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.

This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.

So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).

“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995-1000).

In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292-9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25-50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported financial relationships with several pharmaceutical companies.

Whole-body dual-energy x-ray absorptiometry can provide information on total and regional BMD (left) and body composition (fat and muscle mass).

Source ©ELSEVIER

DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.

“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”

Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra. “This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids, said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis.

Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”

Patient No. 1

A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.

As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.

This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.

So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).

“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995-1000).

In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292-9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25-50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported financial relationships with several pharmaceutical companies.

Whole-body dual-energy x-ray absorptiometry can provide information on total and regional BMD (left) and body composition (fat and muscle mass).

Source ©ELSEVIER

DENVER — People on long-term glucocorticoids have a significant risk for fracture at relatively high bone mineral density T scores. As a result, physicians need to rethink their management of this population.

“In glucocorticoid osteoporosis, the fracture risk seems to take off quite dramatically somewhere around T scores of −1.5,” Dr. Philip Sambrook said during a clinical roundtable session on glucocorticoid-induced osteoporosis at the annual meeting of the American Society for Bone and Mineral Research. “Most of the guidelines around the world are now suggesting that the intervention threshold [for those on glucocorticoids] should be [a T score of] about −1.5.”

Patients on glucocorticoids typically have midline fractures of the vertebrae, where the bone just collapses in the middle of the vertebra. “This is different from the anterior wedge fracture that occurs most commonly in postmenopausal women with osteoporosis,” noted Dr. Nancy Lane, who also participated in the roundtable session. This is because there are some differences in how bones become fragile in the presence of glucocorticoids, said Dr. Lane, who is the director of the center for healthy aging at the University of California, Davis.

Dr. Sambrook, who heads the bone and joint group at the Kolling Institute of Medical Research of Royal North Shore Hospital in Sydney, presented cases that “really illustrate the type of patients that we often struggle with.”

Patient No. 1

A 66-year-old woman was recently diagnosed with polymyalgia rheumatica. She had been started on 25 mg/day prednisone and the disease activity lessened in response. Her history included chronic atopic dermatitis and hypothyroidism. She had no other medical problems. There was no family history of hip fracture. She did not smoke or drink. She had a slightly early menopause but had not used hormone therapy. She reported consuming one or two servings of dairy products daily. She also considered herself to be physically active, although she had no formal exercise program.

As part of her work-up, she had a spine x-ray, which showed a vertebral deformity (compression). BMD measurements showed modest osteopenia (T scores of −1.5 at the spine and −1.6 at the hip). She had normal levels of calcium and parathyroid hormone (PTH). Her vitamin D level was equivocal, however. Her thyroid function was normal.

This patient had modest osteopenia at the time of her diagnosis. Once she was started on glucocorticoids, her T scores could have fallen rapidly and then stabilized over time, without treatment for bone loss, said Dr. Sambrook. “As she becomes established on glucocorticoids, she will perhaps not lose that much bone,” but she's at risk of fracture.

So, when clinical trial data are interpreted, it's important to keep two clinical scenarios in mind: prevention (when initial rapid loss of bone is to be avoided) and treatment (when the patient is on chronic glucocorticoids and may not be losing a lot of bone but is still at risk for fracture).

“Most of us would believe that vitamin D [plus] calcium is an adjunctive therapy,” said Dr. Sambrook. The data appear to back that up. In a 1996 trial, patients with glucocorticoid osteoporosis were randomized to 50,000 U/week of vitamin D plus 1,000 mg/day of calcium, or placebo. Both groups lost bone at the spine quite rapidly, although there was a trend for patients on vitamin D and calcium to do slightly better (J. Rheumatol. 1996;23:995-1000).

In another study, researchers demonstrated that daily alendronate increases bone density in patients who receive glucocorticoid therapy, compared with those on placebo (N. Engl. J. Med. 1998;339:292-9). Similar results have been demonstrated with etidronate, risedronate, and zoledronic acid.

Dr. Sambrook recommended that the patient receive calcium and vitamin D supplementation. Also, “we would primarily give her bisphosphonates until prednisone is discontinued” and possibly beyond, depending on her overall fracture risk after prednisone treatment.

Patient No. 2

A 24-year-old woman has had systemic lupus erythematosus for 3 years, and the disease has become severe over that time. Her SLE complications have included encephalitis, vasculitis, renal involvement, and deep vein thrombosis. She had no family history of osteoporosis. She did not consume much dietary calcium, although she claimed to get adequate sun exposure. She had been on an oral contraceptive since the age of 17. Her appetite and weight were average and stable.

At the time of her presentation, she had been on prednisone for 6 months, with dosages averaging 25-50 mg daily. However, the recent onset of renal complications required increasing the dose to 75 mg daily. She was also taking an antimalaria drug. Her vitamin D level was equivocal and needed to be addressed. She had normal calcium and PTH levels and normal thyroid function. However, her spine T score was −1.4 and her hip T score was −1.0.

The concern to Dr. Sambrook was the effect of bisphosphonates on fetal development. Although the patient was not pregnant at the start of therapy, she might have become so intentionally or unintentionally. Bisphosphonates are classified as pregnancy category C drugs by the U.S. Food and Drug Administration, meaning that they are contraindicated in pregnancy.

One approach to managing this patient is to simply watch her and measure BMD in 12 months. Another is to use a bisphosphonate in conjunction with vitamin D and calcium supplementation. Risedronate might be the better choice, given its quicker onset and offset of action, he said.

“As long as she stayed on prednisone, I might not be as aggressive as with postmenopausal women,” Dr. Sambrook noted. If the prednisone dose was decreased, he said that he might consider stopping bisphosphonate treatment.

Dr. Lane and Dr. Sambrook both reported financial relationships with several pharmaceutical companies.

Whole-body dual-energy x-ray absorptiometry can provide information on total and regional BMD (left) and body composition (fat and muscle mass).

Source ©ELSEVIER