Bisphosphonates are a first choicefor treatingosteoporosis, according to

Kedrin E. Van Steenwyk, DO, an obstetrician/gynecologist

at Sycamore Women’s Center,Miamisburg, Ohio. They are

also first-line drugs for osteoporosisprevention. But not all bisphosphonates

are created equal, observes Melicien A.Tettambel, DO, professor and chair, Maternal

and Child Health, Still University, Kirksville Collegeof Osteopathic Medicine, Kirksville, Mo.

December 2005 13AOA Health Watch

Making intelligentdrug choices

14 AOA Health Watch December 2005

Etidronate, for example, has a track record of increasing bone mineraldensity and decreasing vertebralfractures. However, the Food and Drug Administration never approved the drug for this indication. In fact,other bisphosphonates surged inpopularity when providers questionedetidronate’s role in causing osteomalacia.

Taken daily, weekly or monthlydepending on the formulation (see treatment box, pages 16-17),bisphosphonates are approved for the prevention and treatment ofosteoporosis.

On deck, says Dr. Tettambel, are other bisphosphonates includingzoledronic acid, which would be taken once annually.

Selective estrogen receptormodulators (SERMs), such as raloxifeneand tamoxifen, generate estrogen-likeeffects while apparently decreasingpossible effects that can lead to breastcancer. Approved by the FDA for theprevention and treatment of osteoporosis,raloxifene is probably less effective than bisphosphonates or estrogen in preventing bone loss.

While Dr. Van Steenwyk believeshormone therapy is an excellenttreatment for osteoporosis in thepostmenopausal woman, she believesthat each woman “must be counseled on the risks and benefits of HT therapy,including the possible increased risks forcardiovascular events and breast cancer.”

“Candidates for combined estrogen-progestin therapy includepostmenopausal women with seriousmenopausal symptoms and women who need medication for osteoporosisbut who can’t tolerate other drugs,” adds Dr. Tettambel.

How does estrogen therapy compare

with bisphosphonates and SERMS inreducing fracture risk? The jury is stillout. However, the Women’s HealthInitiative (WHI) discovered thatcombined estrogen-progestin treatmentreduces hip and vertebral fracture risk by 34%. Reduced fracture risk

was also observed in the WHI trial of unopposed estrogen.

Together with parathyroid hormone, calcitonin helps to regulatecalcium concentrations in the body.Physicians who recommend calcitoninfor treating osteoporosis typicallysuggest administration through an easy-to-use nasal spray. This serves as an alternative to injections, which can lead to nausea, vomiting andflushing in patients.

Physicians often recommend otherdrugs over calcitonin (since no one iscompletely sure that calcitonin increasesbone density and decreases fractures

outside the spine.) would change this to read ... data does not supportcalcitionins ability to decrease non-vertebral fractures. However, manyphysicians find the analgesic effects ofcalcitonin are useful in treating patientswho experience sudden, acute pain froma vertebral fracture. “Physicians changethe treatment when the acute painsubsides or when the pain fails tosubside within four weeks,” says Dr. Tettambel.

Produced by the parathyroid glands, parathyroid hormone (PTH)stimulates resorption and new boneformation. Administered intermittently,the drug stimulates formation more than resorption, while it also works to prevent and treat osteoporosis. One preparation, teraperitide has earned FDA approval as the firstanabolic agent for the treatment of osteoporosis.

“While this preparation is moreeffective than other treatments inbuilding spine bone density, it calls fordaily injections and comes at a highprice,” says Dr. Van Steenwyk. “For thisreason, physicians reserve it for treatingthe most severe cases of osteoporosis.”

How do physicians evaluate theeffectiveness of a hormone or drugtherapy? They measure a patient’sbone mineral density, while evaluatingbiochemical markers that signal boneturnover. Typically, physicians measurebone density and biochemical markersat the onset of therapy and follow upwith a second series of biochemicalmarker tests within three months. If the hormone or drug therapygenerates beneficial effects, physicianstend to continue it, scheduling arepeat bone density measurementwithin two years.

It is important for osteopathic physicians toindividualize osteoporosis treatments andbecome familiar with the various treatmentoptions—their use, risks and side effects.

December 2005 15AOA Health Watch

To test or not to testPhysicians should consider bone density testing for women who are age 65 or older; women who are 60 with an increased risk of osteoporosis;postmenopausal women who haverecently fractured a bone; and youngerpostmenopausal women with other risk factors for osteoporosis.

A woman’s risk of osteoporosisincreases if she is white; has a history of falls or bone fractures as an adult;smokes; has an early onset of menopause;is alcoholic; has low calcium and vitaminD intake; has low body weight; does notget enough physical activity; had a lateonset of first menstrual cycle; has lowestrogen levels; has muscle weakness;consumes a lot of caffeine; or has afamily history of osteoporosis.

If your patient is Medicare eligible, the Bone Mass Measurement Act of 1998 provides Medicarereimbursement of bone density testing.Repeat measurements can be doneevery two years and more often forpatients on steroid therapy or furthermedical indications.

The US government has orderedMedicare to pay for bone density testing in the following instances:◗ If your patient is postmenopausal

and at risk of osteoporosis.◗ If your patient has primary

hyperparathyroidism.◗ If your patient has certain

spinal abnormalities that might indicate a fracture.

◗ If your patient is on long-termcorticosteroid therapy, such as prednisone.

◗ If you are assessing a patient’s response to osteoporosis medications.

Final notesTesting for osteoporosis no longer meansjust informing your patients about theirfates. Test results now provide aframework so physicians can work withpatients to build a treatment strategy.

The best defense against osteoporosisis a healthy lifestyle: a diet rich incalcium, regular exercise, limited alcoholintake and no smoking; but for patientswho have one or more risk factors, there are other preventative measuresthat can be considered.

Breakthroughs in the prevention and treatment of osteoporosis continueas do the technological advances intesting. In addition, several drugs havebeen shown to stop and even reversebone loss. Osteopathic physicians mustcontinue to work with their patients todetermine the best path of treatmentand to educate them about preventingand treating osteoporosis.

How is it prescribed?◗ Prevention dose—

35 mg once a week or 5 mg daily.

◗ Treatment dose—70 mg once a week or 10 mg daily.

New formulation—Fosamax with vitamin D once weekly. Should be taken on an empty stomach with a full glass of water.Patients must be able to sit upright or stand for at least 30 minutes after ingesting medication.

What’s the buzz?Side effects include abdominal pain,nausea, heartburn, musculoskeletal pain and very rarely esophageal orgastric ulcers. Contraindicated inpatients with hypocalcemia.

Need more information?Check out:Fosamax.comwww.nlm.nih.gov/medlinepluswww.medicinenet.com

16 AOA Health Watch December 2005

What’s the treatment?Bisphosphonate:Risedronate, Actonel

What has it been shown to do?◗ Reduce fractures at the spine

and hip-within six months, with antifracture, efficacydemonstrated to five years.

◗ Increase and maintain bone density for seven years.

How is it prescribed?◗ 5 mg daily or 35 mg once a week.◗ New formulation—Actonel with

calcium is FDA approved.◗ Indicated for the prevention and

treatment of osteoporosis inpostmenopausal women andprevention and treatment ofglucocorticoid induced osteoporosisin men and women and treatment of Paget’s disease.

◗ Should be taken in the morning on an empty stomach with a full glass of water.

◗ Patients must sit up or stand for 30minutes after ingesting medication.

What’s the buzz?Side effects include abdominal pain,nausea, heartburn, musculoskeletal pain,and very rarely esophageal or gastriculcers. Contraindicated in patients with hypocalemia.

Need more information?Check out: Actonel.comwww.medicinenet.comwww.rxlist.com

What’s the treatment?Bisphosphonate:Ibandronate, Boniva

What has it been shown to do?◗ Reduce vertebral fractures

in postmenopausal women.

Currently, FDA-approved therapies are divided into twogroups: antiresorptive therapy and anabolic therapy.

Antiresorptive Therapies

What’s the treatment?Bisphosphonate:Alendronate, Fosamax

What has it been shown to do?◗ Reduce fractures at the spine,

hip and forearm.◗ Increase and maintain bone

density for 10 years.◗ Indication: Prevention and

treatment of osteoporosis inpostmenopausal women and treatment of glucocorticoid induced osteoporosis in men andwomen, treatment of men withosteoporosis and Paget’s disease.

What’s the buzz?The FDA has limited its use to twoyears due to an increased incidence of osteosarcoma that was seen inearlier animal studies. No such tumors have been seen in humantrials. Side effects include nausea, leg cramps, hypotension and transienthypercalcemia. Contraindicated inpatients with Paget’s disease, boneymetastases, skeletal malignancy,hypercalcemia, and unexplainedelevations in alkaline phosphatase.

Need more information?Check out:www.hsc.wvu.eduwww.fda.gov/bbs/topicswww.forteo.com

Anabolic Therapies

What’s the treatment?Parathyroid Hormone:Teriparatide, Forteo

What has it been shown to do?◗ Decrease vertebral and

non-vertebral fractures. ◗ Indicated for postmenopausal

women, men at high risk for fracture and women with osteoporosis who have multiple risk factors for fracture or who have fractured previously.

How is it prescribed?◗ Given as a daily injection of 20 mg

subcutaneously. Forteo should berefrigerated when not in use.

December 2005 17AOA Health Watch

How is it prescribed?◗ 2.5 mg oral daily tablet

or a 150 mg oral tablet monthly.◗ Should be taken on an empty

stomach with a full glass of water.Do not crush or suck tablet.

◗ Patients must be able to sit up or stand for 60 minutes afteringesting the medication.

What’s the buzz?Side effects include abdominal pain,nausea, heartburn, musculoskeletal pain and esophageal irritation.Contraindicated in patients with hypocalcemia.

Need more information?4boniva.comwwwnlm.nih.gov/medlineplus

What’s the treatment?Calcitonin:Miacalcin Fortical

What has it been shown to do?◗ Reduce vertebral fractures

in women five years post menopause with osteoporosis.

How is it prescribed?◗ Given as a single daily nasal

spray of 200 IUs or a daily subcutaneous injection.

What’s the buzz?Side effects to the nasal spray includenasal irritation and runny or bloodynose. Side effects to the injectioninclude nausea, headache and vomiting. Maicalcin nasal spray isrecommended with adequate calcium(1000 mg elemental calcium)per day and vitamin D (400 IU) per day.

Need more information?Check out:www.miacalcin.comwww.medicinenet.comwww.nlm.nih.gov/medlineplus

What’s the treatment?ET (estrogen therapy)HT(menopausal hormone

therapy)

What has it been shown to do?◗ Prevent osteoporosis in

postmenopausal women.

How is it prescribed?◗ Hormone therapy needs to be

individualized to the patient. In 2003 the FDA issued the followingrecommendations: Consider all non-estrogen preparations first; prescribe the smallest dose for the shortestamount of time to achieve treatmentgoals; prescribe ET/HT products onlywhen the benefits outweigh the risks.

What’s the buzz?A May 2002 Women’s Health Initiativestudy showed that if 10,000 women were prescribed Conjugated EquineEstrogen/Medroxyprogesterone Acetate(CEE/MPA) at a dose equivalent to .625 to 2.5 mg daily, there would be seven more cardiac events, eight more strokes, 18 more venousthromboembolic events, eight moreinvasive breast cancers, six fewercolorectal cancers, five fewer hip fractures, and five fewer vertebral fractures.

Need more information?nia.nih.gov/NR/rdonlyreswww.medicinenet.comwww.medscape.com

What’s the treatment?Selective Estrogen Receptor Modulators:Raloxifene, Evista®

What has it been shown to do?◗ Acts as an estrogen agonist on

bone but as an estrogen antagonist on both the breast and uterus.

◗ Indicated for the prevention and treatment of osteoporosis inpostmenopausal women. Reducesvertebral fractures in patients with and without history of vertebral fracture.

How is it prescribed?Taken as a 60 mg tablet once a day with or without meals.

What’s the buzz?Side effects include hot flashes, leg cramps and increased incidence of venous thromboembolism (VTE).Contraindicated in patients with a history of or active thrombotic disease and in women who may become pregnant; Raloxifene should be discontinued 72 hours prior toprolonged immbolization, such as sugery, bed rest or long flights.Evista has had positive effect on lipid profiles lowering total and LDL cholesterol.

Need more information?Check out:www.nlm.nih.gov/medlineplusraloxifene.drugs.com

ResourcesInternet Drug News.com(Osteoporosis and Paget’s Disease Drug Database) www.coreynahman.com/osteoporosis_pagets.html

Osteoporosis: Drugs Used to Treat Osteoporosis www.endocrineweb.com/osteoporosis/drugs.html

Osteoporosis Drug Therapy www.mayoclinic.org

Osteoporosis Treatment www.emedicinehealth.com

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