Limited Bone Loss With Low-dose Glucocorticoids

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PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).

Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.

All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.

Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.

Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.

"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.

The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.

"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.

Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.

Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.

"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.

Dr. Boers his coinvestigators reported having no financial conflicts.

[email protected]

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest. 

PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).

Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.

All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.

Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.

Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.

"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.

The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.

"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.

Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.

Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.

"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.

Dr. Boers his coinvestigators reported having no financial conflicts.

[email protected]

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the posttest. 

PARIS – Bone loss at 1 year is limited at the low doses of glucocorticoids typically used to treat adults with chronic inflammatory disorders like rheumatoid arthritis, based on a meta-analysis of prospective studies of 1,565 patients with chronic inflammatory diseases (44 studies) and 635 transplant patients (16 studies).

Glucocorticoid treatment at the high doses used in transplantation patients leads to considerable bone loss, especially in the lumbar spine. In contrast, bone loss is limited during glucocorticoid treatment at the lower doses used in chronic inflammatory disease, Dr. Maarten Boers, professor of clinical epidemiology at VU University Medical Center, Amsterdam, reported at the annual European Congress of Rheumatology.

All patients in the meta-analysis had at least two bone mineral density (BMD) measurements over at least 8 months. None received bisphosphonates or antiresorptive therapies, only vitamin D3 and calcium were allowed.

Glucocorticoid doses ranged from 1 to 16 mg/day (mean 9 mg/day) in the patients with chronic inflammatory diseases and from 6 to 53 mg/day (mean 20 mg/day) in the transplant patients. In those with chronic inflammatory diseases, bone loss at the lumbar spine at 1 year averaged –1.7%. For the patients who had measures of femoral neck bone loss, the average loss was –1.3%. In the transplantation group, average bone loss was much higher at –3.6% in the lumbar spine and –3.1% in the femoral neck.

Among the 44 studies that reported BMD in patients with chronic inflammatory diseases, BMD declined from baseline in the lumbar spine by as much as 6% in 1 study and increased by as much as 2% in another. The 39 studies that also reported changes in femoral neck BMD described a decline as high as 7% and an increase as great as 4%.

"We sought to quantify the ‘pure’ effect of GC [glucocorticoid(s)], because so little high-quality information is available," Dr. Boers explained.

The data analysis in these studies was limited to 1 year, but about two-thirds of the patients with chronic inflammatory disease were on chronic glucocorticoid therapy and almost all of the transplant patients were just starting glucocorticoids, Dr. Boers said.

"On average, the yearly loss in a wide range of doses is limited, but starters have more bone loss. The heterogeneity of studies suggests that factors other than GC dose are the main drivers in determining bone loss. Although the data were not available to study these factors, it appears likely that disease activity is very important and acts as a confounder. In other words, disease activity leads to bone loss, and high GC doses lead to bone loss. Effective treatment of high disease activity requires high GC doses, but the interaction of these factors may lead to bone loss comparable to low disease activity being treated with low doses," he explained in an interview.

Many rheumatoid arthritis patients are initially treated with "bridge" glucocorticoid therapy for a few months, until the effect of methotrexate is established, he said. "We prefer ‘COBRA [combination therapy for rheumatoid arthritis] light,’ where patients are initially treated with a higher dose of 30 mg, rapidly tapered to 7.5 mg/day, and maintained for at least 6 months. Several groups are advising to treat for longer periods, and observational data suggest many patients are kept on chronic therapy for periods longer than 1 year," he said.

Local guidelines differ, but all guidelines agree on the necessity of prophylaxis in high-risk situations and on screening for intermediate-risk patients. Unfortunately, many patients requiring antiresorptive treatment according to the guidelines are still not receiving it, with surveys showing about 70% uptake in patients treated by rheumatologists and only about 30% in patients receiving care from other specialists, he said.

"Given the effects of starting GC therapy in our review, we strongly suggest all patients requiring GC therapy for longer than 3 months at any dose should at least be assessed by DXA scan; postmenopausal women, males age 70 or older, and patients with other risk factors should be treated with antiresorptive agents from the start," Dr. Boers advised.

Dr. Boers his coinvestigators reported having no financial conflicts.

[email protected]

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.