Teriparatide Now Preferred Drug for Steroid-Induced Osteoporosis

SAN DIEGO – Teriparatide has received a boost in status as a preferentially effective treatment for glucocorticoid-induced osteoporosis in the form of a second, confirmatory, randomized double-blind trial demonstrating the anabolic agent achieves substantially greater increases in bone mineral density compared to a bisphosphonate.

One of these studies also included fracture rates as a preplanned secondary endpoint; the trial demonstrated a significant reduction in vertebral fractures with teriparatide (Forteo) as compared to alendronate (Fosamax).

These positive study findings are bolstered by a biologically plausible mechanism of benefit, Dr. Kenneth G. Saag observed at the annual meeting of the American Society for Bone and Mineral Research.

"Based upon the pathogenesis of glucocorticoid-induced osteoporosis [(GIOP)], we think that an anabolic agent makes some sense. It may be beneficial to stimulate osteoblasts to promote new bone formation," said Dr. Saag, professor of medicine and epidemiology at the University of Alabama at Birmingham.

Steroids are known to have apoptosis-mediated deleterious effects on both osteocytes and osteoblasts that lead to decline in bone function and an abrupt increase in fracture risk independent of bone mineral density (BMD). Osteoclasts are also unfavorably impacted due to crosstalk and the indirect effects of sex steroids, insulin-like growth factor, and a modest effect of secondary hyperparathyroidism mediated through altered calcium absorption. In addition, higher-dose steroids have adverse effects upon muscle that can independently lead to a higher fracture rate, the rheumatologist explained.

The FDA has approved alendronate, zoledronic acid (Reclast), and risedronate (Actonel) for treatment GIOP. More recently, raloxifene (Evista) has joined the ranks of agents shown to increase BMD in patients on long-term steroids; this came in the form of a double-blind, placebo-controlled, 12-month study (Ann. Rheum. Dis. 2011;70:778-84).

Subcutaneous daily teriparatide for up to 2 years also has the approval of the Food and Drug Administration for use in adults at high fracture risk because they are on sustained systemic steroid therapy.

There is no definitive study demonstrating that any of these agents actually prevents fractures in patients with GIOP. Nor is it likely such a study will be undertaken. Such trials require large numbers of patients and lengthy follow-up, and pharmaceutical companies have little incentive to mount such a costly project given that the medications are already approved for use in patients on steroids, Dr. Saag noted.

However, data from a study in which Dr. Saag was lead investigator showed that teriparatide-treated patients had significantly fewer vertebral fractures than those assigned to alendronate. The study was a 36-month randomized, double-blind, clinical trial that assessed fracture rates as a preplanned secondary endpoint. The radiographic and clinical vertebral fracture rates in 169 alendronate-treated patients were 7.7% and 2.4%, respectively, compared to 1.7% and 0% in 173 teriparatide-treated patients (P = .007 and .037). No significant difference in nonvertebral fractures was found between the two treatment arms.

The primary study endpoint was the change in BMD from baseline. Here again teriparatide proved significantly more effective than the bisphosphonate, with a mean 11% increase at the lumbar spine, compared to 5.3% with alendronate. Teriparatide-treated patients also had a 5.2% increase in BMD at the total hip and a 6.3% boost at the femoral neck, compared to 2.7% and 3.4%, respectively, with alendronate (Arthritis Rheum. 2009;60:3346-55).

Confirmation of teriparatide’s superior BMD-building effect came from the EuroGIOPs trial presented by Dr. Claus C. Glüer at the ASBMR meeting.

EuroGIOPS was an 18-month, open-label, phase III clinical trial in which 92 men with GIOP were randomized to teriparatide or risedronate. At 6 months the mean increase in lumbar spine BMD was 5.7% in the teriparatide group, compared with 3.3% in the risedronate arm. At 18 months – the primary study endpoint – the teriparatide group averaged a 16.3% BMD increase over baseline, while the risedronate arm had a 3.8% rise.

Intriguingly, new clinical fractures occurred during 18 months of therapy in 5 patients on risedronate and none on teriparatide, a difference that came within a hair of statistical significance (P = .056).

Bone strength as formally measured in terms of anterior bending, axial compression, and axial torsion was also significantly greater in the teriparatide group, according to Dr. Glüer, who is professor of medical physics at the department of diagnostic radiology, University Hospital Schleswig-Holstein in Kiel, Germany.

The 2010 update of the American College of Rheumatology guidelines for the prevention and treatment of GIOP recommend bisphosphonates but not teriparatide for older adults at high risk of fracture who are taking less than 5 mg/day of prednisone for less than 1 month (Arthritis Care Res. 2010;62:1515-26). The ACR guidelines recommend reserving use of teriparatide for high-risk patients – that is, those with a prevalent fracture or a World Health Organization Fracture Risk Assessment Tool (FRAX) score indicative of a greater than 20% 10-year risk of a major osteoporotic fracture – who are on at least 6 mg/day of prednisone for less than 1 month or on any dose of glucocorticoids for longer than 1 month.

Although Dr. Saag was a coauthor of the ACR guidelines, he disagreed with this particular one in light of his own clinical trial findings as well as evidence that BMD loss and fracture risk increase early on after starting steroids, and at lower doses than previously thought problematic. So he was pleased to see a new commentary on the ACR guidelines published by the Professional Practice Committee of the ASBMR. The review recommends teriparatide or any of the bisphosphonates for high-risk patients, period.

Dr. Saag, who wasn’t involved in the ASBMR review, recommended it as useful reading both for its areas of agreement with the ACR guidelines as well as for raising several patient scenarios in which the ASBMR committee believes the ACR recommendations either don’t apply or might be improved upon.

The ASBMR commentary also lays out a research agenda, identifying key areas for future study. For example, what’s the best management strategy in lupus patients and others who may need to be on systemic steroids for a decade or more, given that teriparatide is only FDA approved for 2 years of daily use and the clinical trials of bisphosphonates for GIOPS were only 1 or 2 years long (J. Bone Miner. Res. 2011;26:1989-96).

Dr. Glüer declared having no financial conflicts regarding the Eli Lilly-funded EuroGIOPs trial. Dr. Saag disclosed that he has received research grants from and serves as a paid consultant to Amgen, Eli Lilly, Merck, and Novartis.

SAN DIEGO – Teriparatide has received a boost in status as a preferentially effective treatment for glucocorticoid-induced osteoporosis in the form of a second, confirmatory, randomized double-blind trial demonstrating the anabolic agent achieves substantially greater increases in bone mineral density compared to a bisphosphonate.

One of these studies also included fracture rates as a preplanned secondary endpoint; the trial demonstrated a significant reduction in vertebral fractures with teriparatide (Forteo) as compared to alendronate (Fosamax).

These positive study findings are bolstered by a biologically plausible mechanism of benefit, Dr. Kenneth G. Saag observed at the annual meeting of the American Society for Bone and Mineral Research.

"Based upon the pathogenesis of glucocorticoid-induced osteoporosis [(GIOP)], we think that an anabolic agent makes some sense. It may be beneficial to stimulate osteoblasts to promote new bone formation," said Dr. Saag, professor of medicine and epidemiology at the University of Alabama at Birmingham.

Steroids are known to have apoptosis-mediated deleterious effects on both osteocytes and osteoblasts that lead to decline in bone function and an abrupt increase in fracture risk independent of bone mineral density (BMD). Osteoclasts are also unfavorably impacted due to crosstalk and the indirect effects of sex steroids, insulin-like growth factor, and a modest effect of secondary hyperparathyroidism mediated through altered calcium absorption. In addition, higher-dose steroids have adverse effects upon muscle that can independently lead to a higher fracture rate, the rheumatologist explained.

The FDA has approved alendronate, zoledronic acid (Reclast), and risedronate (Actonel) for treatment GIOP. More recently, raloxifene (Evista) has joined the ranks of agents shown to increase BMD in patients on long-term steroids; this came in the form of a double-blind, placebo-controlled, 12-month study (Ann. Rheum. Dis. 2011;70:778-84).

Subcutaneous daily teriparatide for up to 2 years also has the approval of the Food and Drug Administration for use in adults at high fracture risk because they are on sustained systemic steroid therapy.

There is no definitive study demonstrating that any of these agents actually prevents fractures in patients with GIOP. Nor is it likely such a study will be undertaken. Such trials require large numbers of patients and lengthy follow-up, and pharmaceutical companies have little incentive to mount such a costly project given that the medications are already approved for use in patients on steroids, Dr. Saag noted.

However, data from a study in which Dr. Saag was lead investigator showed that teriparatide-treated patients had significantly fewer vertebral fractures than those assigned to alendronate. The study was a 36-month randomized, double-blind, clinical trial that assessed fracture rates as a preplanned secondary endpoint. The radiographic and clinical vertebral fracture rates in 169 alendronate-treated patients were 7.7% and 2.4%, respectively, compared to 1.7% and 0% in 173 teriparatide-treated patients (P = .007 and .037). No significant difference in nonvertebral fractures was found between the two treatment arms.

The primary study endpoint was the change in BMD from baseline. Here again teriparatide proved significantly more effective than the bisphosphonate, with a mean 11% increase at the lumbar spine, compared to 5.3% with alendronate. Teriparatide-treated patients also had a 5.2% increase in BMD at the total hip and a 6.3% boost at the femoral neck, compared to 2.7% and 3.4%, respectively, with alendronate (Arthritis Rheum. 2009;60:3346-55).

Confirmation of teriparatide’s superior BMD-building effect came from the EuroGIOPs trial presented by Dr. Claus C. Glüer at the ASBMR meeting.

EuroGIOPS was an 18-month, open-label, phase III clinical trial in which 92 men with GIOP were randomized to teriparatide or risedronate. At 6 months the mean increase in lumbar spine BMD was 5.7% in the teriparatide group, compared with 3.3% in the risedronate arm. At 18 months – the primary study endpoint – the teriparatide group averaged a 16.3% BMD increase over baseline, while the risedronate arm had a 3.8% rise.

Intriguingly, new clinical fractures occurred during 18 months of therapy in 5 patients on risedronate and none on teriparatide, a difference that came within a hair of statistical significance (P = .056).

Bone strength as formally measured in terms of anterior bending, axial compression, and axial torsion was also significantly greater in the teriparatide group, according to Dr. Glüer, who is professor of medical physics at the department of diagnostic radiology, University Hospital Schleswig-Holstein in Kiel, Germany.

The 2010 update of the American College of Rheumatology guidelines for the prevention and treatment of GIOP recommend bisphosphonates but not teriparatide for older adults at high risk of fracture who are taking less than 5 mg/day of prednisone for less than 1 month (Arthritis Care Res. 2010;62:1515-26). The ACR guidelines recommend reserving use of teriparatide for high-risk patients – that is, those with a prevalent fracture or a World Health Organization Fracture Risk Assessment Tool (FRAX) score indicative of a greater than 20% 10-year risk of a major osteoporotic fracture – who are on at least 6 mg/day of prednisone for less than 1 month or on any dose of glucocorticoids for longer than 1 month.

Although Dr. Saag was a coauthor of the ACR guidelines, he disagreed with this particular one in light of his own clinical trial findings as well as evidence that BMD loss and fracture risk increase early on after starting steroids, and at lower doses than previously thought problematic. So he was pleased to see a new commentary on the ACR guidelines published by the Professional Practice Committee of the ASBMR. The review recommends teriparatide or any of the bisphosphonates for high-risk patients, period.

Dr. Saag, who wasn’t involved in the ASBMR review, recommended it as useful reading both for its areas of agreement with the ACR guidelines as well as for raising several patient scenarios in which the ASBMR committee believes the ACR recommendations either don’t apply or might be improved upon.

The ASBMR commentary also lays out a research agenda, identifying key areas for future study. For example, what’s the best management strategy in lupus patients and others who may need to be on systemic steroids for a decade or more, given that teriparatide is only FDA approved for 2 years of daily use and the clinical trials of bisphosphonates for GIOPS were only 1 or 2 years long (J. Bone Miner. Res. 2011;26:1989-96).

Dr. Glüer declared having no financial conflicts regarding the Eli Lilly-funded EuroGIOPs trial. Dr. Saag disclosed that he has received research grants from and serves as a paid consultant to Amgen, Eli Lilly, Merck, and Novartis.

SAN DIEGO – Teriparatide has received a boost in status as a preferentially effective treatment for glucocorticoid-induced osteoporosis in the form of a second, confirmatory, randomized double-blind trial demonstrating the anabolic agent achieves substantially greater increases in bone mineral density compared to a bisphosphonate.

One of these studies also included fracture rates as a preplanned secondary endpoint; the trial demonstrated a significant reduction in vertebral fractures with teriparatide (Forteo) as compared to alendronate (Fosamax).

These positive study findings are bolstered by a biologically plausible mechanism of benefit, Dr. Kenneth G. Saag observed at the annual meeting of the American Society for Bone and Mineral Research.

"Based upon the pathogenesis of glucocorticoid-induced osteoporosis [(GIOP)], we think that an anabolic agent makes some sense. It may be beneficial to stimulate osteoblasts to promote new bone formation," said Dr. Saag, professor of medicine and epidemiology at the University of Alabama at Birmingham.

Steroids are known to have apoptosis-mediated deleterious effects on both osteocytes and osteoblasts that lead to decline in bone function and an abrupt increase in fracture risk independent of bone mineral density (BMD). Osteoclasts are also unfavorably impacted due to crosstalk and the indirect effects of sex steroids, insulin-like growth factor, and a modest effect of secondary hyperparathyroidism mediated through altered calcium absorption. In addition, higher-dose steroids have adverse effects upon muscle that can independently lead to a higher fracture rate, the rheumatologist explained.

The FDA has approved alendronate, zoledronic acid (Reclast), and risedronate (Actonel) for treatment GIOP. More recently, raloxifene (Evista) has joined the ranks of agents shown to increase BMD in patients on long-term steroids; this came in the form of a double-blind, placebo-controlled, 12-month study (Ann. Rheum. Dis. 2011;70:778-84).

Subcutaneous daily teriparatide for up to 2 years also has the approval of the Food and Drug Administration for use in adults at high fracture risk because they are on sustained systemic steroid therapy.

There is no definitive study demonstrating that any of these agents actually prevents fractures in patients with GIOP. Nor is it likely such a study will be undertaken. Such trials require large numbers of patients and lengthy follow-up, and pharmaceutical companies have little incentive to mount such a costly project given that the medications are already approved for use in patients on steroids, Dr. Saag noted.

However, data from a study in which Dr. Saag was lead investigator showed that teriparatide-treated patients had significantly fewer vertebral fractures than those assigned to alendronate. The study was a 36-month randomized, double-blind, clinical trial that assessed fracture rates as a preplanned secondary endpoint. The radiographic and clinical vertebral fracture rates in 169 alendronate-treated patients were 7.7% and 2.4%, respectively, compared to 1.7% and 0% in 173 teriparatide-treated patients (P = .007 and .037). No significant difference in nonvertebral fractures was found between the two treatment arms.

The primary study endpoint was the change in BMD from baseline. Here again teriparatide proved significantly more effective than the bisphosphonate, with a mean 11% increase at the lumbar spine, compared to 5.3% with alendronate. Teriparatide-treated patients also had a 5.2% increase in BMD at the total hip and a 6.3% boost at the femoral neck, compared to 2.7% and 3.4%, respectively, with alendronate (Arthritis Rheum. 2009;60:3346-55).

Confirmation of teriparatide’s superior BMD-building effect came from the EuroGIOPs trial presented by Dr. Claus C. Glüer at the ASBMR meeting.

EuroGIOPS was an 18-month, open-label, phase III clinical trial in which 92 men with GIOP were randomized to teriparatide or risedronate. At 6 months the mean increase in lumbar spine BMD was 5.7% in the teriparatide group, compared with 3.3% in the risedronate arm. At 18 months – the primary study endpoint – the teriparatide group averaged a 16.3% BMD increase over baseline, while the risedronate arm had a 3.8% rise.

Intriguingly, new clinical fractures occurred during 18 months of therapy in 5 patients on risedronate and none on teriparatide, a difference that came within a hair of statistical significance (P = .056).

Bone strength as formally measured in terms of anterior bending, axial compression, and axial torsion was also significantly greater in the teriparatide group, according to Dr. Glüer, who is professor of medical physics at the department of diagnostic radiology, University Hospital Schleswig-Holstein in Kiel, Germany.

The 2010 update of the American College of Rheumatology guidelines for the prevention and treatment of GIOP recommend bisphosphonates but not teriparatide for older adults at high risk of fracture who are taking less than 5 mg/day of prednisone for less than 1 month (Arthritis Care Res. 2010;62:1515-26). The ACR guidelines recommend reserving use of teriparatide for high-risk patients – that is, those with a prevalent fracture or a World Health Organization Fracture Risk Assessment Tool (FRAX) score indicative of a greater than 20% 10-year risk of a major osteoporotic fracture – who are on at least 6 mg/day of prednisone for less than 1 month or on any dose of glucocorticoids for longer than 1 month.

Although Dr. Saag was a coauthor of the ACR guidelines, he disagreed with this particular one in light of his own clinical trial findings as well as evidence that BMD loss and fracture risk increase early on after starting steroids, and at lower doses than previously thought problematic. So he was pleased to see a new commentary on the ACR guidelines published by the Professional Practice Committee of the ASBMR. The review recommends teriparatide or any of the bisphosphonates for high-risk patients, period.

Dr. Saag, who wasn’t involved in the ASBMR review, recommended it as useful reading both for its areas of agreement with the ACR guidelines as well as for raising several patient scenarios in which the ASBMR committee believes the ACR recommendations either don’t apply or might be improved upon.

The ASBMR commentary also lays out a research agenda, identifying key areas for future study. For example, what’s the best management strategy in lupus patients and others who may need to be on systemic steroids for a decade or more, given that teriparatide is only FDA approved for 2 years of daily use and the clinical trials of bisphosphonates for GIOPS were only 1 or 2 years long (J. Bone Miner. Res. 2011;26:1989-96).

Dr. Glüer declared having no financial conflicts regarding the Eli Lilly-funded EuroGIOPs trial. Dr. Saag disclosed that he has received research grants from and serves as a paid consultant to Amgen, Eli Lilly, Merck, and Novartis.