Re: INFO - Preventing steroid-induced osteoporosis

April 8, 2005

Yikes . I didn't realize that the bone loss was immediate!!! How

can they allow steroids to be prescribed for RA yet ban the -2's for

problems not as serious as with steroids? I'll never understand why so

many rheumatologists get their patients hooked on steroids knowing the

serious side effects.

a

On Apr 8, 2005, at 7:48 AM, wrote:

> Preventing glucocorticoid-induced osteoporosis

>

> Sep 15, 2002

> Patient Care

>

> Bone loss from glucocorticoid therapy is immediate and occurs

> at the

> highest rate during the first 6 months. Judicious use of calcium,

> vitamin D,

> hormone replacement therapy, and bisphosphonates at the onset of

> long-term

> treatment can improve bone density.

>

> Exogenous glucocorticoids are the treatment of choice for many

> medical

> conditions, and their beneficial effects can be quite dramatic. Yet

> this

> class of drugs is potentially one of the most toxic, with side effects

> ranging from less serious medical conditions such as truncal obesity,

> striae, and cataracts, to more serious ones such as hypertension,

> diabetes

> mellitus, osteonecrosis, and osteoporosis. Glucocorticoids have been

> a known

> risk factor for osteoporosis since the 1930s, when their association

> with

> skeletal changes and endocrine tumors was first reported.1

>

> By the 1950s, exogenous glucocorticoid therapy became

> widespread, and

> the severity of glucocorticoid-induced osteoporosis (GIO) was more

> fully

> appreciated. Recent data suggest that osteoporosis will develop in

> approximately 50% of patients who undergo long-term glucocorticoid

> therapy,

> thereby increasing their risk of sustaining spontaneous fractures.2

> Long-term therapy with 7.5 mg/d of prednisone is associated with an

> average

> of 3% bone loss annually. Despite its prevalence and significant

> morbidity,

> this common iatrogenic disease is often underrecognized and

> inadequately

> treated. This article will review the problem and suggest solutions.

>

> HOW GLUCOCORTICOIDS CAUSE BONE LOSS

>

> Bone is actively remodeled throughout adult life. Even in the

> absence

> of glucocorticoid exposure, 25% of trabecular bone and 3% of cortical

> bone

> are remodeled annually.

>

> Osteoblasts and osteoclasts are the cell types largely

> responsible for

> bone turnover. Osteoblasts are cuboidal cells found in clusters at

> the bone

> surface. They produce a layer of osteoid, which matures over a period

> of 10

> days by a process of calcification that, over the course of several

> months,

> results in new bone. Osteoclasts are multinucleated giant cells

> responsible

> for bone resorption. They attach to bone matrix via integrin

> receptors,

> which help to create pockets of extracellular space bordered by folds

> of

> ruffled osteoclast membrane. This process creates secondary lysosomes

> characterized by a low pH and an enzyme-rich environment in which bone

> matrix degradation occurs. When glucocorticoids cause bone resorption

> to

> occur at a faster rate than bone formation, osteoporosis results.

>

> Corticosteroid receptors are partitioned into two types:

> mineralocorticoid (found in CNS and renal tissue) and glucocorticoid

> (present in virtually all cells of the body). Glucocorticoid receptors

> mediate both the anti-inflammatory and metabolic effects of

> corticosteroids.

> When glucocorticoids bind to the cellular receptors, the resulting

> complex

> migrates to the nucleus where gene expression is induced.

> Consequently, all

> levels of the inflammatory cascade are inhibited. Glucocorticoids are

> most

> effective at suppressing T lymphocytes and natural killer cells, but

> they

> tend to be less effective at inhibiting mature B cells.

> Corticosteroids also

> suppress proinflammatory cytokines such as tumor necrosis

> factor-alpha and

> interleukin-1. They have inhibitory effects on inflammatory mediators

> such

> as gamma interferon, prostaglandin E2, and leukotrienes. The overall

> result

> appears to be preferential suppression of cellular immunity rather

> than

> humoral immunity.

>

> GIO occurs as a consequence of multiple direct and indirect

> effects of

> glucocorticoids on bone formation and resorption, the metabolism of

> calcium

> and vitamin D, and the modulation of sex hormones. Glucocorticoids

> directly

> inhibit osteoblast proliferation and matrix synthesis and cause a

> decline in

> circulating levels of osteocalcin. They have also been implicated in

> osteoblast apoptosis. Since bone formation is linked to body mass and

> muscle

> strength, the catabolic effects of corticosteroids on muscle may

> indirectly

> reduce bone formation. Hence, glucocorticoids weaken bone formation

> by way

> of a glucocorticoid-induced myopathy with its associated loss of the

> trophic

> effect of muscle stress on bone.

>

> Corticosteroids also reduce sex hormone levels. They

> specifically

> suppress estrogen, luteinizing hormone, and follicle-stimulating

> hormone in

> women, which normally act to inhibit bone resorption. Moreover, a

> loss of

> estrogen is associated with a net increase in numbers of osteoclasts.

> The

> resultant hypogonadism favors osteoclastic over osteoblastic activity.

>

> In addition, glucocorticoids may indirectly accelerate bone

> resorption

> by causing excessive calciuria. The reduced availability of substrate

> for

> bone formation that results is worsened by impaired renal tubular

> reabsorption of calcium caused by glucocorticoids as well as reduced

> serum

> levels of 1,25-dihydroxyvitamin D. This net loss in calcium causes a

> secondary hyperparathyroidism, leading to further resorption of bone.3

> Furthermore, glucocorticoids also decrease trabecular bone mass by

> interfering with bone-active cytokines such as insulinlike growth

> factors.

>

> GIO becomes detectable by sensitive radiologic methods as early

> as 1

> month into systemic glucocorticoid therapy. Dual-energy x-ray

> absorptiometry

> (DXA) and quantitative CT are radiologic methods available for

> detecting low

> bone mass. Of these techniques, DXA is less expensive and more widely

> available. T-scores, which are used in clinical decision-making,

> represent

> the number of standard deviations below or above the peak bone mass

> in a

> young adult reference population of the same sex. According to the

> World

> Health Organization, a T-score above -1 reflects normal bone density,

> between -1 and -2.5 is osteopenia, and below -2.5 signifies

> osteoporosis.3 A

> T-score below -2.5 in addition to a personal history of fractures

> indicates

> severe osteoporosis.

>

> Individuals at greatest risk for GIO are those experiencing

> high bone

> turnover or those with a preexisting imbalance between resorption and

> formation, including children aged 15 and younger, adults older than

> 50,

> postmenopausal women, and immobilized patients. Bone loss occurs

> mostly in

> areas of high turnover, such as trabecular bone of the vertebra, and

> resulting spontaneous fractures commonly involve the vertebrae or

> ribs.4,5

> In one study, current corticosteroid users were 2.7 times more likely

> to

> sustain a hip fracture compared with nonusers.6

>

> Significant metabolic bone disease due to glucocorticoid therapy

> occurs in a short amount of time. Even low-dose, 6-week corticosteroid

> treatment is associated with adverse effects on bone metabolism.7 In

> one

> study, 10 mg/d of prednisone over a 2-month period adversely affected

> calcium and bone metabolism by uncoupling bone formation and

> resorption.7

> Another study found that 20 weeks of treatment with low-dose

> prednisone

> induced a mean trabecular bone mineral density decline of 8.2% in

> patients

> with rheumatoid arthritis.8 Susceptibility to fracture is dependent on

> dosage, and the overall risk of fracture is increased during oral

> corticosteroid therapy, becoming apparent within the first 3 months of

> treatment.9 Therefore, preventive therapy for osteoporosis should

> commence

> when glucocorticoids are first prescribed.2

>

> PROPHYLAXIS AGAINST GIO

>

> Early strategies for the prevention and treatment of GIO

> blunted the

> adverse impact of steroids on bone but did not consistently improve

> bone

> strength, as has been seen with the more recently released class of

> agents

> known as bisphosphonates. Among those strategies were sodium

> restriction

> with concurrent thiazide diuretic therapy and treatment with sodium

> fluoride

> or calcitonin. In particular, the use of thiazide diuretics with salt

> restriction remains of unproved benefit, while treatment with vitamin

> D

> carries a risk of hypercalciuria and urinary stone formation. Sodium

> fluoride stimulates bone formation but remains controversial because

> of the

> resultant abnormal bone quality noted during such therapy.10

>

> Over the past decade, however, some notable inroads toward the

> reduction of corticosteroid-induced bone mineral loss were made.11-15

> Most

> notably, these include gonadal hormone supplementation and

> bisphosphonates,

> both of which have antiresorptive properties and may maintain or

> increase

> bone density in some persons taking corticosteroids. Calcitonin can be

> effective in some cases and may be considered when bisphosphonates

> are not a

> viable option.

>

> In addition to using those therapies, the American College of

> Rheumatology (ACR) recommends treating confounding comorbid

> conditions such

> as hyperthyroidism.2 Lifestyle alterations that may improve bone

> health

> include exercise, reduction of alcohol use, and avoidance of

> cigarettes.

> Although the best preventive measure is to discontinue use of

> glucocorticoids, in many situations this course of action is not

> feasible.

> Glucocorticoids should be prescribed at the minimum effective dose.

> Topical

> or inhaled agents are preferred over systemic corticosteroids, if

> practical.

> Because bone loss is most rapid during the first 6 months of

> glucocorticoid

> therapy, the ACR advises physicians to start all patients on calcium

> plus

> vitamin D at the onset of treatment.

>

> Calcitonin and vitamin D metabolites

> Providing adequate substrate for bone formation includes

> supplementation with calcium in addition to vitamin D. A daily intake

> of

> 1500 mg of elemental calcium, either through diet or supplements,

> reduces

> bone turnover. In most patients, cholecalciferol, 400 to 800 IU/d, is

> sufficient to maintain serum levels in a proper range. If high-dose

> cholecalciferol is used, carefully check both serum and urine calcium

> levels

> periodically.

>

> Intranasal salmon calcitonin administered in dosages up to 400

> IU/d

> was shown in several studies to blunt the loss of bone mineral

> content.10

> One study comparing prophylactic use of calcium, calcitriol, and

> calcitonin

> found that only treatment with calcium and calcitriol (with or without

> calcitonin) prevented or reduced bone loss from the lumbar spine.15 A

> significant side effect of treatment was hypercalcemia. Variable

> dosing of

> corticosteroid therapy and the lack of a placebo control group,

> however, may

> limit interpretation of results of this particular study. Expert

> consultation should be obtained before prescribing calcitriol.

>

> Hormone replacement therapy

>

> Corticosteroids reduce levels of sex hormones, thereby

> indirectly

> facilitating osteoclastic bone resorption. Therefore, patients taking

> glucocorticoids may benefit from hormone replacement therapy (HRT), a

> strategy that is still being investigated. One study using gonadal

> hormone

> replacement for patients receiving chronic glucocorticoid therapy

> demonstrated either stability or improvement of bone mineral density

> in both

> men and women.16

>

> Bisphosphonates

>

> Synthetic pyrophosphates that resist chemical

> degradation-bisphosphonates-have recently become key players in

> treating and

> preventing GIO. A study assessing the benefit of alendronate for

> patients on

> long-term corticosteroid therapy found that those taking alendronate

> showed

> increased bone mineral density in the lumbar spine, hips, and overall

> compared to patients taking placebo.12 In addition, fewer new

> vertebral

> fractures were observed in the alendronate group. The evidence

> suggests that

> prophylaxis with alendronate, 5 mg/d, may be warranted in patients

> receiving

> long-term glucocorticoids. More recently, a third-generation oral

> bisphosphonate was shown to prevent bone loss in patients initiating

> corticosteroid treatment. Risedronate, 5 mg/d, resulted in significant

> positive treatment effects in both men and women after 12 months of

> intervention.13 Other bisphosphonates that may help treat or prevent

> GIO

> include IV pamidronate and the cyclical administration of etidronate.

>

> Anabolic therapy

>

> Recently, anabolic therapy, with parathyroid hormone in

> particular,

> has shown promise in the treatment of GIO.17 Early studies, however,

> do not

> reveal consistent improvement throughout the skeleton, and primary

> prevention studies are yet to be completed.

>

> EVIDENCE OF UNDERTREATMENT

>

> Despite recent guidelines published by the ACR and numerous

> studies

> establishing the efficacy of preventive therapy against GIO, growing

> evidence suggests widespread underutilization of these measures. A

> telephone

> survey of patients on long-term glucocorticoids reported that 29% were

> taking calcium supplements and 45% were receiving vitamin D. Of the

> postmenopausal women surveyed, 40% were receiving HRT, 14% were

> receiving

> bisphosphonates, and 29% had undergone a DXA scan.18 In another study,

> charts of 215 clinic patients on glucocorticoid therapy for more than

> 1

> month were reviewed. Prophylaxis against GIO was prescribed for 58%

> of the

> patients.10

>

> The rheumatology staff at The Washington University

> Medical

> Center, Washington, DC, performed a similar retrospective chart

> review. In

> this unpublished study, only 29% of the patients surveyed were given

> preventive therapy, and only 16% were assessed via DXA scan. All of

> the

> patients evaluated and given prophylaxis were women, most of whom

> were in

> their 40s. Preventive therapy was typically initiated after the

> patient had

> taken glucocorticoids for more than 2 years and at dosages equivalent

> to

> more than 10 mg/d of prednisone. The results showed that even

> university-based rheumatologists who commonly confront the adverse

> effects

> of excess exogenous glucocorticoids infrequently evaluate for, or

> provide

> prophylaxis against, GIO.

>

> A history of a DXA scan correlated with a higher rate of

> preventive

> therapy by increasing the likelihood of diagnosing GIO. Therefore,

> increasing physician awareness concerning issues surrounding GIO may

> be of

> significant importance in detecting and treating patients with

> metabolic

> bone disease. These studies show the need to initiate a better

> approach to

> educate patients and physicians regarding the importance of GIO

> prevention.

>

> A checklist addressing issues pertinent to patients taking

> glucocorticoids, such as adverse effects of corticosteroids, risk

> factors

> for osteoporosis, previous DXA scan results, and preventive therapy

> selected, may be a useful tool for physicians (see " Monitoring

> patients on

> glucocorticoids " ). This type of document can be placed in the charts

> of all

> patients when initiating glucocorticoid therapy to serve as a

> reminder of

> the increased risk of osteoporosis and the need for prophylaxis.

>

> EDITED BY STACY DILORETO

>

> REFERENCES

>

> 1. Cushing H. Basophile adenomas of the pituitary body. J Nerv

> Ment

> Dis. 1932;76:50-56.

>

> 2. American College of Rheumatology Task Force on Osteoporosis

> Guidelines. Recommendations for the prevention and treatment of

> glucocorticoid-induced osteoporosis. Arthritis Rheum.

> 1996;39:1791-1801.

>

> 3. NOF Physician's Guide: Diagnosis. National Osteoporosis

> Foundation

> Web site. Available at: http://www.nof.org/physguide/diagnosis.htm .

> Accessed October 9, 2000.

>

> 4. Seeman E, Wahner HW, Offord KP, et al. Differential effects

> of

> endocrine dysfunction on the axial and the appendicular skeleton. J

> Clin

> Invest. 1982;69:1302-1309.

>

> 5. Lane NE, Mroczkowski PJ, Hochberg MC. Prevention and

> management of

> glucocorticoid-induced osteoporosis. Bull Rheum Dis. 1995;44:1-4.

>

> 6. C, Coupland C, M. Rheumatoid arthritis,

> corticosteroid therapy and hip fracture. Ann Rheum Dis. 1995;54:49-52.

>

> 7. Lems WF, s JW, Van Rijn HJ, et al. Changes in calcium

> and bone

> metabolism during treatment with low dose prednisone in young,

> healthy, male

> volunteers. Clin Rheumatol. 1995;14:420-424.

>

> 8. Laan RF, van Riel PL, van de Putte LB, et al. Low-dose

> prednisone

> induces rapid reversible axial bone loss in patients with rheumatoid

> arthritis. Ann Intern Med. 1993;119:963-968.

>

> 9. Van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral

> corticosteroids and risk of fractures. J Bone Miner Res.

> 2000;15:993-1000.

>

> 10. Eastell R, Reid DM, Compston J, et al. A UK Consensus Group

> on

> management of glucocorticoid-induced osteoporosis: an update. J

> Intern Med.

> 1998;244:271-292.

>

> 11. Boutsen Y, Jamart J, Esselinckx W, et al. Primary

> prevention of

> glucocorticoid-induced osteoporosis with intermittent intravenous

> pamidronate: a randomized trial. Calcif Tissue Int. 1997;61:266-271.

>

> 12. Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the

> prevention and treatment of glucocorticoid-induced osteoporosis.

> Glucocorticoid-Induced Osteoporosis Study Group. N Engl J Med.

> 1998;339:292-299.

>

> 13. Cohen S, Levy RM, Keller M, et al. Risedronate therapy

> prevents

> corticosteroid-induced bone loss: a twelve-month, multicenter,

> randomized,

> double-blind, placebo-controlled, parallel-group study. Arthritis

> Rheum.

> 1999;42:2309-2318.

>

> 14. Buckley LM, Leib ES, Cartularo KS, et al. Calcium and

> vitamin D3

> supplementation prevents bone loss in the spine secondary to low-dose

> corticosteroids in patients with rheumatoid arthritis: a randomized,

> double-blind, placebo-controlled trial. Ann Intern Med.

> 1996;125:961-968.

>

> 15. Sambrook P, Birmingham J, P, et al. Prevention of

> corticosteroid osteoporosis: a comparison of calcium, calcitrol, and

> calcitonin. N Engl J Med. 1993;328:1747-1752.

>

> 16. Lukert BP, BE, RG. Estrogen and

> progesterone

> replacement therapy reduces glucocorticoid-induced bone loss. J Bone

> Miner

> Res. 1992;7:1063-1069.

>

> 17. Lane NE, S, Genant HK, et al. Short-term increases

> in bone

> turnover markers predict parathyroid hormone-induced spinal bone

> mineral

> density gains in postmenopausal women with glucocorticoid-induced

> osteoporosis. Osteoporos Int. 2000;11:434-442.

>

> 18. Aagaard EM, Lin P, Modin GW, et al. Prevention of

> glucocorticoid-induced osteoporosis: provider practice at an urban

> county

> hospital. Am J Med. 1999;107:456-460.

>

> ARTICLE CONTRIBUTORS

> DEBORAH T. ZAREK, MD, Internal Medicine Resident, Christiana

> Care

> Health System-Christiana Hospital, Newark, Del.

> JAMES D. KATZ, MD, Assistant Professor of Medicine, Division of

> Rheumatology, The Washington University Medical Center,

> Washington,

> DC.

>

> http://www.patientcareonline.com/patcare/article/articleDetail.jsp?

> id=117083

>

> Not an MD

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

April 8, 2005

Yikes . I didn't realize that the bone loss was immediate!!! How

can they allow steroids to be prescribed for RA yet ban the -2's for

problems not as serious as with steroids? I'll never understand why so

many rheumatologists get their patients hooked on steroids knowing the

serious side effects.

a

On Apr 8, 2005, at 7:48 AM, wrote:

> Preventing glucocorticoid-induced osteoporosis

>

> Sep 15, 2002

> Patient Care

>

> Bone loss from glucocorticoid therapy is immediate and occurs

> at the

> highest rate during the first 6 months. Judicious use of calcium,

> vitamin D,

> hormone replacement therapy, and bisphosphonates at the onset of

> long-term

> treatment can improve bone density.

>

> Exogenous glucocorticoids are the treatment of choice for many

> medical

> conditions, and their beneficial effects can be quite dramatic. Yet

> this

> class of drugs is potentially one of the most toxic, with side effects

> ranging from less serious medical conditions such as truncal obesity,

> striae, and cataracts, to more serious ones such as hypertension,

> diabetes

> mellitus, osteonecrosis, and osteoporosis. Glucocorticoids have been

> a known

> risk factor for osteoporosis since the 1930s, when their association

> with

> skeletal changes and endocrine tumors was first reported.1

>

> By the 1950s, exogenous glucocorticoid therapy became

> widespread, and

> the severity of glucocorticoid-induced osteoporosis (GIO) was more

> fully

> appreciated. Recent data suggest that osteoporosis will develop in

> approximately 50% of patients who undergo long-term glucocorticoid

> therapy,

> thereby increasing their risk of sustaining spontaneous fractures.2

> Long-term therapy with 7.5 mg/d of prednisone is associated with an

> average

> of 3% bone loss annually. Despite its prevalence and significant

> morbidity,

> this common iatrogenic disease is often underrecognized and

> inadequately

> treated. This article will review the problem and suggest solutions.

>

> HOW GLUCOCORTICOIDS CAUSE BONE LOSS

>

> Bone is actively remodeled throughout adult life. Even in the

> absence

> of glucocorticoid exposure, 25% of trabecular bone and 3% of cortical

> bone

> are remodeled annually.

>

> Osteoblasts and osteoclasts are the cell types largely

> responsible for

> bone turnover. Osteoblasts are cuboidal cells found in clusters at

> the bone

> surface. They produce a layer of osteoid, which matures over a period

> of 10

> days by a process of calcification that, over the course of several

> months,

> results in new bone. Osteoclasts are multinucleated giant cells

> responsible

> for bone resorption. They attach to bone matrix via integrin

> receptors,

> which help to create pockets of extracellular space bordered by folds

> of

> ruffled osteoclast membrane. This process creates secondary lysosomes

> characterized by a low pH and an enzyme-rich environment in which bone

> matrix degradation occurs. When glucocorticoids cause bone resorption

> to

> occur at a faster rate than bone formation, osteoporosis results.

>

> Corticosteroid receptors are partitioned into two types:

> mineralocorticoid (found in CNS and renal tissue) and glucocorticoid

> (present in virtually all cells of the body). Glucocorticoid receptors

> mediate both the anti-inflammatory and metabolic effects of

> corticosteroids.

> When glucocorticoids bind to the cellular receptors, the resulting

> complex

> migrates to the nucleus where gene expression is induced.

> Consequently, all

> levels of the inflammatory cascade are inhibited. Glucocorticoids are

> most

> effective at suppressing T lymphocytes and natural killer cells, but

> they

> tend to be less effective at inhibiting mature B cells.

> Corticosteroids also

> suppress proinflammatory cytokines such as tumor necrosis

> factor-alpha and

> interleukin-1. They have inhibitory effects on inflammatory mediators

> such

> as gamma interferon, prostaglandin E2, and leukotrienes. The overall

> result

> appears to be preferential suppression of cellular immunity rather

> than

> humoral immunity.

>

> GIO occurs as a consequence of multiple direct and indirect

> effects of

> glucocorticoids on bone formation and resorption, the metabolism of

> calcium

> and vitamin D, and the modulation of sex hormones. Glucocorticoids

> directly

> inhibit osteoblast proliferation and matrix synthesis and cause a

> decline in

> circulating levels of osteocalcin. They have also been implicated in

> osteoblast apoptosis. Since bone formation is linked to body mass and

> muscle

> strength, the catabolic effects of corticosteroids on muscle may

> indirectly

> reduce bone formation. Hence, glucocorticoids weaken bone formation

> by way

> of a glucocorticoid-induced myopathy with its associated loss of the

> trophic

> effect of muscle stress on bone.

>

> Corticosteroids also reduce sex hormone levels. They

> specifically

> suppress estrogen, luteinizing hormone, and follicle-stimulating

> hormone in

> women, which normally act to inhibit bone resorption. Moreover, a

> loss of

> estrogen is associated with a net increase in numbers of osteoclasts.

> The

> resultant hypogonadism favors osteoclastic over osteoblastic activity.

>

> In addition, glucocorticoids may indirectly accelerate bone

> resorption

> by causing excessive calciuria. The reduced availability of substrate

> for

> bone formation that results is worsened by impaired renal tubular

> reabsorption of calcium caused by glucocorticoids as well as reduced

> serum

> levels of 1,25-dihydroxyvitamin D. This net loss in calcium causes a

> secondary hyperparathyroidism, leading to further resorption of bone.3

> Furthermore, glucocorticoids also decrease trabecular bone mass by

> interfering with bone-active cytokines such as insulinlike growth

> factors.

>

> GIO becomes detectable by sensitive radiologic methods as early

> as 1

> month into systemic glucocorticoid therapy. Dual-energy x-ray

> absorptiometry

> (DXA) and quantitative CT are radiologic methods available for

> detecting low

> bone mass. Of these techniques, DXA is less expensive and more widely

> available. T-scores, which are used in clinical decision-making,

> represent

> the number of standard deviations below or above the peak bone mass

> in a

> young adult reference population of the same sex. According to the

> World

> Health Organization, a T-score above -1 reflects normal bone density,

> between -1 and -2.5 is osteopenia, and below -2.5 signifies

> osteoporosis.3 A

> T-score below -2.5 in addition to a personal history of fractures

> indicates

> severe osteoporosis.

>

> Individuals at greatest risk for GIO are those experiencing

> high bone

> turnover or those with a preexisting imbalance between resorption and

> formation, including children aged 15 and younger, adults older than

> 50,

> postmenopausal women, and immobilized patients. Bone loss occurs

> mostly in

> areas of high turnover, such as trabecular bone of the vertebra, and

> resulting spontaneous fractures commonly involve the vertebrae or

> ribs.4,5

> In one study, current corticosteroid users were 2.7 times more likely

> to

> sustain a hip fracture compared with nonusers.6

>

> Significant metabolic bone disease due to glucocorticoid therapy

> occurs in a short amount of time. Even low-dose, 6-week corticosteroid

> treatment is associated with adverse effects on bone metabolism.7 In

> one

> study, 10 mg/d of prednisone over a 2-month period adversely affected

> calcium and bone metabolism by uncoupling bone formation and

> resorption.7

> Another study found that 20 weeks of treatment with low-dose

> prednisone

> induced a mean trabecular bone mineral density decline of 8.2% in

> patients

> with rheumatoid arthritis.8 Susceptibility to fracture is dependent on

> dosage, and the overall risk of fracture is increased during oral

> corticosteroid therapy, becoming apparent within the first 3 months of

> treatment.9 Therefore, preventive therapy for osteoporosis should

> commence

> when glucocorticoids are first prescribed.2

>

> PROPHYLAXIS AGAINST GIO

>

> Early strategies for the prevention and treatment of GIO

> blunted the

> adverse impact of steroids on bone but did not consistently improve

> bone

> strength, as has been seen with the more recently released class of

> agents

> known as bisphosphonates. Among those strategies were sodium

> restriction

> with concurrent thiazide diuretic therapy and treatment with sodium

> fluoride

> or calcitonin. In particular, the use of thiazide diuretics with salt

> restriction remains of unproved benefit, while treatment with vitamin

> D

> carries a risk of hypercalciuria and urinary stone formation. Sodium

> fluoride stimulates bone formation but remains controversial because

> of the

> resultant abnormal bone quality noted during such therapy.10

>

> Over the past decade, however, some notable inroads toward the

> reduction of corticosteroid-induced bone mineral loss were made.11-15

> Most

> notably, these include gonadal hormone supplementation and

> bisphosphonates,

> both of which have antiresorptive properties and may maintain or

> increase

> bone density in some persons taking corticosteroids. Calcitonin can be

> effective in some cases and may be considered when bisphosphonates

> are not a

> viable option.

>

> In addition to using those therapies, the American College of

> Rheumatology (ACR) recommends treating confounding comorbid

> conditions such

> as hyperthyroidism.2 Lifestyle alterations that may improve bone

> health

> include exercise, reduction of alcohol use, and avoidance of

> cigarettes.

> Although the best preventive measure is to discontinue use of

> glucocorticoids, in many situations this course of action is not

> feasible.

> Glucocorticoids should be prescribed at the minimum effective dose.

> Topical

> or inhaled agents are preferred over systemic corticosteroids, if

> practical.

> Because bone loss is most rapid during the first 6 months of

> glucocorticoid

> therapy, the ACR advises physicians to start all patients on calcium

> plus

> vitamin D at the onset of treatment.

>

> Calcitonin and vitamin D metabolites

> Providing adequate substrate for bone formation includes

> supplementation with calcium in addition to vitamin D. A daily intake

> of

> 1500 mg of elemental calcium, either through diet or supplements,

> reduces

> bone turnover. In most patients, cholecalciferol, 400 to 800 IU/d, is

> sufficient to maintain serum levels in a proper range. If high-dose

> cholecalciferol is used, carefully check both serum and urine calcium

> levels

> periodically.

>

> Intranasal salmon calcitonin administered in dosages up to 400

> IU/d

> was shown in several studies to blunt the loss of bone mineral

> content.10

> One study comparing prophylactic use of calcium, calcitriol, and

> calcitonin

> found that only treatment with calcium and calcitriol (with or without

> calcitonin) prevented or reduced bone loss from the lumbar spine.15 A

> significant side effect of treatment was hypercalcemia. Variable

> dosing of

> corticosteroid therapy and the lack of a placebo control group,

> however, may

> limit interpretation of results of this particular study. Expert

> consultation should be obtained before prescribing calcitriol.

>

> Hormone replacement therapy

>

> Corticosteroids reduce levels of sex hormones, thereby

> indirectly

> facilitating osteoclastic bone resorption. Therefore, patients taking

> glucocorticoids may benefit from hormone replacement therapy (HRT), a

> strategy that is still being investigated. One study using gonadal

> hormone

> replacement for patients receiving chronic glucocorticoid therapy

> demonstrated either stability or improvement of bone mineral density

> in both

> men and women.16

>

> Bisphosphonates

>

> Synthetic pyrophosphates that resist chemical

> degradation-bisphosphonates-have recently become key players in

> treating and

> preventing GIO. A study assessing the benefit of alendronate for

> patients on

> long-term corticosteroid therapy found that those taking alendronate

> showed

> increased bone mineral density in the lumbar spine, hips, and overall

> compared to patients taking placebo.12 In addition, fewer new

> vertebral

> fractures were observed in the alendronate group. The evidence

> suggests that

> prophylaxis with alendronate, 5 mg/d, may be warranted in patients

> receiving

> long-term glucocorticoids. More recently, a third-generation oral

> bisphosphonate was shown to prevent bone loss in patients initiating

> corticosteroid treatment. Risedronate, 5 mg/d, resulted in significant

> positive treatment effects in both men and women after 12 months of

> intervention.13 Other bisphosphonates that may help treat or prevent

> GIO

> include IV pamidronate and the cyclical administration of etidronate.

>

> Anabolic therapy

>

> Recently, anabolic therapy, with parathyroid hormone in

> particular,

> has shown promise in the treatment of GIO.17 Early studies, however,

> do not

> reveal consistent improvement throughout the skeleton, and primary

> prevention studies are yet to be completed.

>

> EVIDENCE OF UNDERTREATMENT

>

> Despite recent guidelines published by the ACR and numerous

> studies

> establishing the efficacy of preventive therapy against GIO, growing

> evidence suggests widespread underutilization of these measures. A

> telephone

> survey of patients on long-term glucocorticoids reported that 29% were

> taking calcium supplements and 45% were receiving vitamin D. Of the

> postmenopausal women surveyed, 40% were receiving HRT, 14% were

> receiving

> bisphosphonates, and 29% had undergone a DXA scan.18 In another study,

> charts of 215 clinic patients on glucocorticoid therapy for more than

> 1

> month were reviewed. Prophylaxis against GIO was prescribed for 58%

> of the

> patients.10

>

> The rheumatology staff at The Washington University

> Medical

> Center, Washington, DC, performed a similar retrospective chart

> review. In

> this unpublished study, only 29% of the patients surveyed were given

> preventive therapy, and only 16% were assessed via DXA scan. All of

> the

> patients evaluated and given prophylaxis were women, most of whom

> were in

> their 40s. Preventive therapy was typically initiated after the

> patient had

> taken glucocorticoids for more than 2 years and at dosages equivalent

> to

> more than 10 mg/d of prednisone. The results showed that even

> university-based rheumatologists who commonly confront the adverse

> effects

> of excess exogenous glucocorticoids infrequently evaluate for, or

> provide

> prophylaxis against, GIO.

>

> A history of a DXA scan correlated with a higher rate of

> preventive

> therapy by increasing the likelihood of diagnosing GIO. Therefore,

> increasing physician awareness concerning issues surrounding GIO may

> be of

> significant importance in detecting and treating patients with

> metabolic

> bone disease. These studies show the need to initiate a better

> approach to

> educate patients and physicians regarding the importance of GIO

> prevention.

>

> A checklist addressing issues pertinent to patients taking

> glucocorticoids, such as adverse effects of corticosteroids, risk

> factors

> for osteoporosis, previous DXA scan results, and preventive therapy

> selected, may be a useful tool for physicians (see " Monitoring

> patients on

> glucocorticoids " ). This type of document can be placed in the charts

> of all

> patients when initiating glucocorticoid therapy to serve as a

> reminder of

> the increased risk of osteoporosis and the need for prophylaxis.

>

> EDITED BY STACY DILORETO

>

> REFERENCES

>

> 1. Cushing H. Basophile adenomas of the pituitary body. J Nerv

> Ment

> Dis. 1932;76:50-56.

>

> 2. American College of Rheumatology Task Force on Osteoporosis

> Guidelines. Recommendations for the prevention and treatment of

> glucocorticoid-induced osteoporosis. Arthritis Rheum.

> 1996;39:1791-1801.

>

> 3. NOF Physician's Guide: Diagnosis. National Osteoporosis

> Foundation

> Web site. Available at: http://www.nof.org/physguide/diagnosis.htm .

> Accessed October 9, 2000.

>

> 4. Seeman E, Wahner HW, Offord KP, et al. Differential effects

> of

> endocrine dysfunction on the axial and the appendicular skeleton. J

> Clin

> Invest. 1982;69:1302-1309.

>

> 5. Lane NE, Mroczkowski PJ, Hochberg MC. Prevention and

> management of

> glucocorticoid-induced osteoporosis. Bull Rheum Dis. 1995;44:1-4.

>

> 6. C, Coupland C, M. Rheumatoid arthritis,

> corticosteroid therapy and hip fracture. Ann Rheum Dis. 1995;54:49-52.

>

> 7. Lems WF, s JW, Van Rijn HJ, et al. Changes in calcium

> and bone

> metabolism during treatment with low dose prednisone in young,

> healthy, male

> volunteers. Clin Rheumatol. 1995;14:420-424.

>

> 8. Laan RF, van Riel PL, van de Putte LB, et al. Low-dose

> prednisone

> induces rapid reversible axial bone loss in patients with rheumatoid

> arthritis. Ann Intern Med. 1993;119:963-968.

>

> 9. Van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral

> corticosteroids and risk of fractures. J Bone Miner Res.

> 2000;15:993-1000.

>

> 10. Eastell R, Reid DM, Compston J, et al. A UK Consensus Group

> on

> management of glucocorticoid-induced osteoporosis: an update. J

> Intern Med.

> 1998;244:271-292.

>

> 11. Boutsen Y, Jamart J, Esselinckx W, et al. Primary

> prevention of

> glucocorticoid-induced osteoporosis with intermittent intravenous

> pamidronate: a randomized trial. Calcif Tissue Int. 1997;61:266-271.

>

> 12. Saag KG, Emkey R, Schnitzer TJ, et al. Alendronate for the

> prevention and treatment of glucocorticoid-induced osteoporosis.

> Glucocorticoid-Induced Osteoporosis Study Group. N Engl J Med.

> 1998;339:292-299.

>

> 13. Cohen S, Levy RM, Keller M, et al. Risedronate therapy

> prevents

> corticosteroid-induced bone loss: a twelve-month, multicenter,

> randomized,

> double-blind, placebo-controlled, parallel-group study. Arthritis

> Rheum.

> 1999;42:2309-2318.

>

> 14. Buckley LM, Leib ES, Cartularo KS, et al. Calcium and

> vitamin D3

> supplementation prevents bone loss in the spine secondary to low-dose

> corticosteroids in patients with rheumatoid arthritis: a randomized,

> double-blind, placebo-controlled trial. Ann Intern Med.

> 1996;125:961-968.

>

> 15. Sambrook P, Birmingham J, P, et al. Prevention of

> corticosteroid osteoporosis: a comparison of calcium, calcitrol, and

> calcitonin. N Engl J Med. 1993;328:1747-1752.

>

> 16. Lukert BP, BE, RG. Estrogen and

> progesterone

> replacement therapy reduces glucocorticoid-induced bone loss. J Bone

> Miner

> Res. 1992;7:1063-1069.

>

> 17. Lane NE, S, Genant HK, et al. Short-term increases

> in bone

> turnover markers predict parathyroid hormone-induced spinal bone

> mineral

> density gains in postmenopausal women with glucocorticoid-induced

> osteoporosis. Osteoporos Int. 2000;11:434-442.

>

> 18. Aagaard EM, Lin P, Modin GW, et al. Prevention of

> glucocorticoid-induced osteoporosis: provider practice at an urban

> county

> hospital. Am J Med. 1999;107:456-460.

>

> ARTICLE CONTRIBUTORS

> DEBORAH T. ZAREK, MD, Internal Medicine Resident, Christiana

> Care

> Health System-Christiana Hospital, Newark, Del.

> JAMES D. KATZ, MD, Assistant Professor of Medicine, Division of

> Rheumatology, The Washington University Medical Center,

> Washington,

> DC.

>

> http://www.patientcareonline.com/patcare/article/articleDetail.jsp?

> id=117083

>

> Not an MD

>

> I'll tell you where to go!

>

> Mayo Clinic in Rochester

> http://www.mayoclinic.org/rochester

>

> s Hopkins Medicine

> http://www.hopkinsmedicine.org

>

April 8, 2005

----- Original Message -----

From: " a " <a54@...>

> How can they allow steroids to be prescribed for RA yet ban the -2's

for

problems not as serious as with steroids? I'll never understand why so

many rheumatologists get their patients hooked on steroids knowing the

serious side effects.

What would be the alternative drug? Many diseases such as Sjogren's

Syndrome aren't helped by conventional RA drugs such as Enbrel and Humira.

I think the rheumys know the risks, they just have to weigh them against the

alternatives.

Nina

April 8, 2005

----- Original Message -----

From: " a " <a54@...>

> How can they allow steroids to be prescribed for RA yet ban the -2's

for

problems not as serious as with steroids? I'll never understand why so

many rheumatologists get their patients hooked on steroids knowing the

serious side effects.

What would be the alternative drug? Many diseases such as Sjogren's

Syndrome aren't helped by conventional RA drugs such as Enbrel and Humira.

I think the rheumys know the risks, they just have to weigh them against the

alternatives.

Nina

April 8, 2005

Nina,

If you re-read my post, I specified RA. Steroids have their place in

medicine. They can make the difference between life and death in some

cases and for some medical conditions, especially where there is lung

involvement. The FDA pulls the -2's off the market for far less

risks than what steroids have, yet allow rheumatologists routinely

prescribe steroids for RA.

I've had this list for 7 years and had another one before this one, and

in all these years I've noticed that in way to many cases, newly

diagnosed patients are given steroids. Many remain on them for life

causing other serious medical conditions.

The doctors could prescribe pain medicine rather than steroids for

those in severe pain. Patient education should teach

non-pharmacological pain control through aqua therapy, exercise, diet,

relaxation, meditation, accupunture, biofeedback, guided imagery,

hypnosis, and most of all LAUGHTER! Attitude makes a big difference in

how well we deal with these diseases.

If you read all the research articles and I have sent about

prednisone, you might come to the same conclusion that steroids should

be reserved as a last resort, not a first as it is now.

a

On Apr 8, 2005, at 5:40 PM, Nina wrote:

> ----- Original Message -----

> From: " a " <a54@...>

>

> > How can they allow steroids to be prescribed for RA yet ban the

> -2's

> for

> problems not as serious as with steroids? I'll never understand why

> so

> many rheumatologists get their patients hooked on steroids knowing the

> serious side effects.

>

> What would be the alternative drug? Many diseases such as Sjogren's

> Syndrome aren't helped by conventional RA drugs such as Enbrel and

> Humira.

> I think the rheumys know the risks, they just have to weigh them

> against the

> alternatives.

>

> Nina

>

April 8, 2005

Nina,

If you re-read my post, I specified RA. Steroids have their place in

medicine. They can make the difference between life and death in some

cases and for some medical conditions, especially where there is lung

involvement. The FDA pulls the -2's off the market for far less

risks than what steroids have, yet allow rheumatologists routinely

prescribe steroids for RA.

I've had this list for 7 years and had another one before this one, and

in all these years I've noticed that in way to many cases, newly

diagnosed patients are given steroids. Many remain on them for life

causing other serious medical conditions.

The doctors could prescribe pain medicine rather than steroids for

those in severe pain. Patient education should teach

non-pharmacological pain control through aqua therapy, exercise, diet,

relaxation, meditation, accupunture, biofeedback, guided imagery,

hypnosis, and most of all LAUGHTER! Attitude makes a big difference in

how well we deal with these diseases.

If you read all the research articles and I have sent about

prednisone, you might come to the same conclusion that steroids should

be reserved as a last resort, not a first as it is now.

a

On Apr 8, 2005, at 5:40 PM, Nina wrote:

> ----- Original Message -----

> From: " a " <a54@...>

>

> > How can they allow steroids to be prescribed for RA yet ban the

> -2's

> for

> problems not as serious as with steroids? I'll never understand why

> so

> many rheumatologists get their patients hooked on steroids knowing the

> serious side effects.

>

> What would be the alternative drug? Many diseases such as Sjogren's

> Syndrome aren't helped by conventional RA drugs such as Enbrel and

> Humira.

> I think the rheumys know the risks, they just have to weigh them

> against the

> alternatives.

>

> Nina

>

April 8, 2005

----- Original Message -----

From: " a " <a54@...>

> If you read all the research articles and I have sent about

prednisone, you might come to the same conclusion that steroids should

be reserved as a last resort, not a first as it is now.

I'm well aware of the risks. I researched steroids at length when they were

prescribed to me. Part of what is confusing me is you talk about steroids

for pain. That's not what they are for. They are for inflammation.

Nina

April 8, 2005

----- Original Message -----

From: " a " <a54@...>

> If you read all the research articles and I have sent about

prednisone, you might come to the same conclusion that steroids should

be reserved as a last resort, not a first as it is now.

I'm well aware of the risks. I researched steroids at length when they were

prescribed to me. Part of what is confusing me is you talk about steroids

for pain. That's not what they are for. They are for inflammation.

Nina

April 8, 2005

It's great that you are aware. Many are not and that is one reason I

am so passionate about this subject. When I was first diagnosed back

in the 70's, it is the first thing my rheumy tried to give me. I thank

my physiology professor for enlightening me about steroids and their

risks. Had I not found out from him, I would have taken them. My

doctor never mentioned the risks, he just wrote the prescription.

Since then other doctors have tried to prescribe them to me.

Inflammation is what causes pain, so the pain is treated by reducing

inflammation. But you are 100% right, they aren't prescribed for pain.

But the end result is that they reduce pain. Sorry I confused you.

a

On Apr 8, 2005, at 8:08 PM, Nina wrote:

>

> I'm well aware of the risks. I researched steroids at length when

> they were

> prescribed to me. Part of what is confusing me is you talk about

> steroids

> for pain. That's not what they are for. They are for inflammation.

>

> Nina

>

April 8, 2005