Handout_final

OSTEOPOROSIS MANAGEMENT AND INVESTIGATION David A. Hanley, MD, FRCPC
There is a huge care gap in the management of osteoporosis in this country. As yet unpublished findings fromthe Canadian Multicentre Osteoporosis Study (CaMOS) would suggest that approximately 80% of women, andnearly 100% of men who suffer a fragility fracture do not get assessed or treated for osteoporosis.
RISK ASSESSMENT AND INVESTIGATIONS:
HISTORY:
-
back pain; development of dorsal kyphosis.
menstrual history, use of postmenopausal ovarian hormone therapy.
In males, hypogonadism and alcoholism are important causes of osteoporosis.
diet: calcium intake, use of calcium or vitamin D supplements, lactose intolerance.
lifestyle issues: alcohol intake, inactivity or prolonged periods of bed rest, smoking history, excessivecaffeine intake, weight less than 57 kg. or weight loss after age 25.
medications: glucocorticoids, heparin therapy, anticonvulsants, sedatives (cause falling).
past medical history: previous fractures; increased propensity to fall.
endocrine diseases: hyperthyroidism, hyperparathyroidism, hypogonadism, Cushing’s Syndrome;gastrointestinal disease; anorexia nervosa.
family history of osteoporotic fracture (particularly maternal hip fracture).
PHYSICAL EXAMINATION:Kyphosis, muscle weakness (inability to rise from a chair), impaired visual acuity, other disabilities causing atendency to fall.
all should be normal: complete blood count, serum calcium, alkaline phosphatase (may be elevated inacute recovery from fracture), creatinine, serum protein electrophoresis.
Serum 25-OH Vitamin D if there is a question about the patient’s Vitamin D nutrition.
other more specific markers of calcium or bone metabolism may be helpful in assessing apparent failure torespond to therapy.
X-rays should only be used for identifying fractures.
a bone scan can identify fracture activity.
bone density of the spine and hip by Dual Energy X-ray Absorptiometry (DEXA) is currently the preferredmethod of assessing bone mass and fracture risk, as well as following response to therapy (1). Othermethods, eg. heel ultrasound, are acceptable for assessing fracture risk if DEXA is not available, but prob-ably lack the precision necessary for following response to therapy (2).
in the postmenopausal female osteoporosis has been defined as a lumbar spine or femoral neck DEXAmore than 2.5 standard deviations below the mean value for a same sex young adult (“T-score” of -2.5 orlower). Osteopenia (thin bones) is defined as a bone density between 1.0 and 2.5 standard deviations belowthe young adult mean (3). This definition is being used by many clinicians as a guide to managementdecisions. However, it should not be used as the sole criterion for defining osteoporosis in men and pre-menopausal women.
bone density measurement (BMD) is only indicated if it will affect clinical management decisions.
Osteoporosis experts suggest it is of use in the following clinical situations (1,2,4): To diagnose osteopenia at menopause in selected individuals. The U.S. National Osteoporosis Foundation
recommends BMD measurements for postmenopausal women aged 50-65 with one of the following risk
factors: (i) smoker; (ii) history of fracture after age 40; (iii) family history of osteoporotic fracture
after age 50; (iv) body weight < 57 kg.) (3).
Long Term Care 2001: Medical Directors, Physician Services and New Paradigms of Care
To confirm or deny the diagnosis of osteoporosis in patients with radiologic abnormalities consistent withosteoporosis, eg. radiologic diagnosis of osteopenia or vertebral fractures.
Patients with medical problems known to cause rapid bone loss, such as primary hyperparathyroidism orhigh dose prolonged (greater than three months) glucocorticoid therapy, in order to recommend treatmentoptions (parathyroid surgery or bone-sparing pharmacologic therapy, respectively).
To monitor the response to osteoporosis therapy. However, it should be noted that changes in bone densitymay not reflect therapeutic benefit of a drug. Small increases in bone mass may result in significant fractureprevention benefits, as the strength of bone appears to be proportional to the square of the density.
PREVENTION AND TREATMENT
stop smoking, reduce alcohol and caffeine intake.
Therapies for osteoporosis can be classified as those which prevent bone resorption (anti-resorptive) andthose which stimulate bone formation. At present, all of the drugs approved by the Government of CanadaTherapeutics Products Directorate for osteoporosis therapy (estrogen, alendronate, cyclical etidronate,risedronate, raloxifene, and salmon calcitonin) would be categorized as anti-resorptive in their action.
Because of the coupled nature of bone turnover (bone formation always follows resorption), treatment withanti-resorptive agents results in a general slowing down of bone formation and the overall rate of boneremodeling, while the mandatory coupled bone formation proceeds normally. These agents therefore causean initial increase in bone mass, which eventually plateaus, as the overall rate of bone turnover is markedlyreduced.
ANTI-RESORPTIVE AGENTS:
1. Estrogen (+/-) Progesterone (references 5,6)
Estrogen, with progesterone (if the patient has not had a hysterectomy), is considered the front-line choice
for prevention of osteoporosis in the early postmenopause. Earlier reviews by osteoporosis expert organiza-
tions have made estrogen the first choice treatment of established osteoporosis (definition by BMD +/-
fractures) in older postmenopausal women (1,4). However, most clinicians would now rank the
bisphosphonates and raloxifene ahead of estrogen for older postmenopausal women with estab-
lished osteoporosis, because of the superior clinical trial evidence in preventing fractures.
2.Bisphosphonates (references 7-13)
Etidronate (Didronel, Didrocal), alendronate (Fosamax) and risedronate (Actonel) are approved for preventionand treatment of osteoporosis and also Paget’s Disease of bone. Risedronate appears to be similar toalendronate in anti-fracture efficacy. Other available bisphosphonates such as clodronate (Bonefos, Ostac),pamidronate (Aredia) and zoledronate (Zometa) are presently used in the management of malignancy-associated osteolysis, hypercalcemia, and Paget’s Disease, but have also been used in the treatment ofosteoporosis in small clinical trials of short duration. Cyclical etidronate risedronate and alendronate arealso approved for the prevention and treatment of glucocorticoid-induced osteoporosis in Canada.
Alendronate has also shown to be effective in the treatment of osteoporosis in men.
3. Selective Estrogen Receptor Modulators: Raloxifene (References 14-16)
Raloxifene (Evista) has now been approved for both prevention of postmenopausal bone loss and the treat-ment of established osteoporosis. There is clear clinical trial evidence of prevention of vertebral fractures.
Raloxifene is an estrogen antagonist in breast and uterine tissue, and appears to reduce the incidence ofbreast cancer. It has estrogen-like activity on bone and lipid metabolism. Large clinical trials are currently inprogress to assess raloxifene’s ability to prevent heart disease and breast cancer.
For the person at risk for osteoporosis in the first 5-15 years postmenopause, raloxifene is considered anappropriate first-line choice and alternative to estrogen because, like estrogen, it has beneficial effects onbiochemical risk factors for cardiovascular disease (eg. lipid metabolism). Like estrogen, there is a modestincreased risk of deep vein thrombosis and pulmonary embolism in postmenopausal women usingraloxifene. Raloxifene does not treat menopause symptoms of estrogen deficiency, and will aggravate thevasomotor symptoms (hot flushes) if given too early in menopause. Patients should be warned of this.
4. Calcitonin (Reference 17)
A nasal spray of salmon CT (Miacalcin), 200 units once daily, has been shown to prevent vertebral fractures,and has recently been granted HPB approval for treatment of established osteoporosis with vertebral frac-tures.
5. Combination Therapy? (References 18-20)
Combining a bisphosphonate with estrogen or raloxifene is the subject of several recent or on-going clinicaltrials. Estrogen or raloxifene plus a bisphosphonate has additive or synergistic effects on BMD, but nofracture benefit has yet been demonstrated. If a patient continues to lose BMD while taking estrogen, I mayadd a bisphosphonate without stopping estrogen, but it is not my practice to initiate therapy with thecombination.
6. Glucocorticoid Osteoporosis (Reference 21)
A Canadian group has recently published a review of this problem and proposed a treatment algorithm.
Vertebral Fractures are important! (references 22-26) The major risk factors for osteoporosis are age, bone density, and previous osteoporotic fracture.
With respect to the latter, the importance of vertebral fractures as predictors of future problems cannot be
over-emphasized. It is now clear that the presence of a vertebral fracture places a patient at high risk for
another vertebral fracture within a year of suffering the first fracture, and vertebral fractures have been clearly
associated with high risk of other fractures including hip fractures, morbidity, and even mortality.
CONCLUSION
Most clinicians working in this field hold the position that postmenopausal ovarian hormone therapy remainsthe first choice for prevention of osteoporosis for women in the first 5-10 years after menopause. Raloxifeneis approved for the prevention of postmenopausal bone loss and should be considered a solid alternative toestrogen. Raloxifene also has better randomized controlled clinical trial evidence for fracture prevention thanestrogen.
After age 60-65, the majority view would be bisphosphonate therapy should be chosen over ovarian hormonetherapy for the treatment of osteoporosis (a fragility fracture and/or bone density in the “osteoporosis”range), because of better patient acceptability and far superior randomized placebo controlled clinical trialevidence for fracture prevention. Raloxifene and calcitonin are well tolerated alternatives to bisphosphonatetherapy in the treatment of established osteoporosis.
Long Term Care 2001: Medical Directors, Physician Services and New Paradigms of Care
References
Scientific Advisory Board of the Osteoporosis Society of Canada. Clinical practice guidelines for the diagno- sis and management of osteoporosis. Can Med Assoc J 1996; 155(8):1113-1133.
Osteoporosis Society of Canada: Update on diagnostic technologies. Position paper of the Osteoporosis Society of Canada. Osteoporosis Update 1999; 3(3): 2-7.
Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N: The diagnosis of osteoporosis. J Bone Eddy DM, Johnston CC Jr., Cummings SR, et al, for the National Osteoporosis Foundation. Osteoporosis: review of the evidence for prevention, diagnosis, and treatment and cost-effectiveness analysis. Oste-oporosis Int 1998 Supplement 4.
The Writing Group for the PEPI: Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1996; 276: 1389-96 Villareal DT, Binder EF, Williams DB, Schechtman KB, Yarasheski KE, Kohrt WM. Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial. JAMA. 2001Aug 15;286(7):815-20.
Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral EfficacyWith Risedronate Therapy (VERT) Study Group. JAMA 1999; 282: 1344-52 Adachi JD, Bensen WG, Brown J, et al. Intermittent cyclical etidronate therapy in the prevention of corti- costeroid-induced osteoporosis. N Engl J Med 1997; 337: 382-87.
Saag KG, Emkey R, Schnitzer TJ et al. Alendronate for the prevention and treatment of glucocorticoid osteoporosis. N Engl J Med 1998; 339: 292-299.
10. Storm T, Thamsborg G, Steiniche T, Genant HK, Sorensen OH. Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med1990; 322: 1265-71.
11. Black DM, Cummings SR, Karpf DB, et al: Randomized trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996;348: 1535-41.
12. McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY. Effect of risedronate on the risk of hip fracture in elderly women.
Hip Intervention Program Study Group. N Engl J Med. 2001 Feb 1;344(5):333-40.
13. Orwoll E, Ettinger M, Weiss S, et al: Alendronate for the treatment of osteoporosis in men.
N Engl J Med. 2000 Aug 31;343(9):604-10.
14. Delmas PD, Bjarnason NH, Mitlak BH, et al. Effects of raloxifene on bone mineral density, serum choles- terol concentrations, and uterine endometrium in postmenopausal women. N Engl J Med 1997;337:1641-7 15. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomesof Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282: 637-45 16. Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmeno- pausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.
JAMA 1999; 281: 2189-97 17. Chesnut CH, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in post- menopausal women with established osteoporosis: the prevent recurrence of osteoporotic fracturesstudy. Am J Med. 2000; 109: 267-276.
18. Wimalawansa SJ. A four-year randomized controlled trial of hormone replacement and bisphosphonate, alone or in combination, in women with postmenopausal osteoporosis. Am J Med 1998; 104: 219-26 19. Lindsay R, Cosman F, Lobo RA, et al. Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial. J Clin Endocrinol Metab 1999; 84:3076-81 20. Johnell O, Scheele W, Lu Y, Lakshaman M: Effects of raloxifene(RLX), alendronate (ALN), and RLX+ALN on bone mineral density and biochemical markers of bone turnover in postmenopausal women with os-teoporosis. J Bone Miner Res 1999; 14(Suppl 1): p. S157 (Abstr 1100) 21. Adachi JD, Olszynski WP, Hanley DA, et al: Management of corticosteroid-induced osteoporosis. Seminars in Arthritis and Rheumatism 2000; 29: 228-51.
22. Lindsay R, Silverman SL, Cooper C, et al: Risk of new vertebral fracture in the year following a fracture.
23. Ismail AA, Cockerill W, Cooper C, et al: Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study. Osteoporos Int. 2001; 12:85-90.
24. Cooper C, Atkinson EJ, Jacobsen SJ, et al: Population-based study of survival after osteoporotic fractures.
Am J Epidemiol. 1993 May 1; 137: 1001-5.
25. Center JR, Nguyen TV, Schneider D, et al: Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999 Mar 13; 353: 878-82.
26. Kado DM, Browner WS, Palermo L, et al: Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med. 1999 Jun 14;159: 1215-20.
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