Osteoporosis Int

OSTEOPOROSIS MEDICATIONS
Drug Dose Metabolism Efficacy Interactions Side Effects Cost/Coverage

BISPHOSPHONATES
Alendronate Prevention: Not metabolized BMD in lumbar  absorption with food, Nausea, abdominal $10.06/month
Fosamax 5mg once daily by the liver; 50% spine, femoral neck, antacids, iron, calcium pain, acid regurgitation, (70mg weekly) to
Treatment: excreted renally. and trochanter in headache, constipation, $14.96/month (10
Fosavance 10 mg once daily, OR women with <2.5SD  GI side effects with diarrhea, esophagitis, mg daily) ODB
70mg/2800IU 70mg once weekly below young peak NSAIDS, steroids ulceration
70mg/5600IU adult bone mass Blue Cross -
(Alendronate/Vi (1 hour prior to meals with treatment dose special
tamin D3) or other medications) over 3-4 years. authorization
(Fosavance®
(Merck) risk of vertebral, 70mg/2800 IU-
hip and non- not a benefit)
vertebral fractures
by 35-50% NIHB-prior
authorization
Studied in HIV
population (at 70mg
dose +
calcium/vitamin
D)1,2,3. Benefit in
BMD at 48 weeks,
but studies not
powered to detect 
fractures.
Etidronate 1 tablet daily (400 mg Not metabolized BMD in the lumbar  absorption with food, Nausea, abdominal $19.99/90 days
Didrocal etidronate x14 days by the liver; 50% spine (1-2%) over 1 antacids, iron, calcium pain, acid regurgitation, (ODB)
(Warner then calcium of absorbed dose year headache, constipation,
Chilcott) carbonate 500mg is excreted diarrhea, esophagitis, Blue Cross-
elemental x76 days) renally. risk of vertebral ulceration regular benefit
Unabsorbed fractures
1 hour prior to meals etidronate is NIHB-regular
or other medications reported to be benefit
excreted intact
via the feces (up
to 99%)
Risedronate Prevention/treatment: Not metabolized BMD (See  absorption with food, Nausea, abdominal $9.96/month
Actonel 5mg once daily, OR by the liver; up to Alendronate) antacids, iron, calcium pain, acid regurgitation, (35mg once
Academic copyright. C.Mitry, BSc.Phm., Alice Tseng, Pharm.D., Immunodeficiency Clinic, Toronto General Hospital. Updated by Cara Hills-Nieminen, BSc(Pharm), Edmonton
AB. www.hivclinic.ca June 2011 Page 1 of 7
(Aventis) 35mg weekly, OR 80% excreted in headache, constipation, weekly),
150mg once monthly the urine. risk of vertebral, diarrhea, esophagitis, $27.32/month (5
hip and non- ulceration mg daily),
(1 hour prior to meals vertebral fractures $43.15/month
or other medications) by 35-50% (150 mg once
monthly), ODB
Blue Cross-
special
authorization
(75mg/150mg not
a benefit)
NIHB-prior
approval
(75mg/150mg not
a benefit)
Zoledronic Acid Treatment: Not metabolized BMD (See Theoretical interactions: Within first 3 days of $670.80/injection
Aclasta 5mg IV infusion once by the liver; 39 + alendronate) -  serum calcium with loop infusion: fever, myalgia, ($55.90/month)
(Novartis) yearly 16% excreted in diuretics, aminoglycosides flu-like symptoms, ODB
the urine. risk of vertebral, - nephrotoxicity with NSAIDs arthralgia and
hip and non- and other nephrotoxins (ie. headache (resolve Blue Cross-
vertebral fractures Tenofovir, although no thereafter) special
by 40-70% documented interactions). ? risk of atrial fibrillation authorization
– not a confirmed (only for Paget’s
Studied in HIV association disease)
population.4,5 Benefit
in BMD at 12 NIHB-prior
months, but not authorization
powered to detect  (only for Paget’s
fractures. disease)
ANABOLIC AGENTS
Teriparatide Treatment: Metabolized via BMD in lumber  serum calcium with loop & Nausea, headache, $1400/month (not
Forteo 20mcg SC once daily nonspecific spine, femoral-neck thiazide diuretics arthralgia, leg cramps, covered via ODB)
(Eli Lilly) x24 months proteolytic and whole-body dizziness, pain at
hepatic enzymes Use with caution in digoxin injection site Blue Cross-not a
(no specific CYP risk of vertebral patients - serum calcium benefit
metabolism and non-vertebral may predispose to digitalis Transient
information fractures by 53-65% toxicity. hypercalcemia/ NIHB-not a
available) hypoparathyroidism benefit
Although no reports in
humans, potential risk
of osteosarcoma
ESTROGEN/SERMS
Conjugated 0.3mg or 0.625mg Metabolized by BMD in lumbar Avoid OC use if amprenavir, Abdominal pain, $2.36/month
Estrogen once daily CYP3A4 (30%), spine and hip over 2 or unboosted fosamprenavir. amenorrhea, breast (ODB)
Premarin glucuronidation years. tenderness, depression,
(Wyeth-Ayerst) In general, NNRTIs & diarrhea, edema, Blue Cross-
risk of vertebral, boosted PIs have the fatigue, mennoragia, regular beneft
hip and total potential to decrease oral pulmonary embolism,
osteoporotic contraceptive (OC) weight gain NIHB-regular
fractures. effectiveness (ethinyl benefit
estradiol/ norethidrone
Should only be used acetate/ norgestimate)
as symptomatic mostly through induction of
therapy for relief of CYP 3A4 and/or
menopausal glucuronidation – resulting in
symptoms. Should  Cmax/AUC and potential
be used in the for  OC efficacy7.
smallest dose for the
shortest duration.6 ARVs which may  AUC of
OC: ritonavir8, lopinavir/r,
nelfinavir, darunavir/r9,
tipranavir/r, efavirenz10,
nevirapine11, rilpivirine12
RTV & NFV13 can estrogen

metabolism by 
glucuronidation which may
decrease effectiveness 14,15
ARVs which may  AUC and

OC levels: atazanavir16,
amprenavir, indinavir.
Delavirdine, saquinavir17 and

tenofovir result in no OC
level changes. 18
Please refer to the Oral

Contraceptive and ARV
Drug Interactions chart for
more details
effect of warfarin
Counteract effects of
bromocriptine
metabolism of
cyclosporine, TCA
antidepressants
Raloxifene 60mg once daily Extensive 1st BMD of several No documented ARV Hot flashes, muscle $27.51/month
Evista pass metabolism sites by ~2.5% over interactions with raloxifene, cramps, weight gain, (ODB)
(Eli Lilly) in the liver to 1-2 years however, caution when peripheral edema,
glucuronide use.19-20 myalgia, insomnia, Blue Cross-
conjugates; risk of vertebral breast tenderness, special
No reported CYP fractures Cholestyramine raloxifene abdominal pain, vaginal authorization
metabolism absorption bleeding
NIHB-prior
May alter the effects of  risk of deep vein approval
warfarin (monitor INR) thrombosis, and
pulmonary embolism
(not associated with 
CV risk)
Monoclonal Antibody against RANKL
Denosumab 60mg sc every six N/A ⁭ BMD of several Interactions with other drugs Back pain, $450/dose (not
Prolia® months (self- sites by 5.2-8.8% have not been established. musculoskeletal pain, covered via ODB)
(Amgen) administered injection) over 1-3 years rash, constipation,
infection (ie cellulitis), Blue Cross not a
↓ risk of vertebral, hypercholesterolemia, benefit
hip and non- hypocalcemia
vertebral fractures in NIHB not a
postmenoposal benefit
women
CALCITONIN
Calcitonin 200IU intranasal once Metabolized Stabilizes BMD in No significant drug $64.69/month
Calcimar daily primarily in the lumbar spine and hip interactions reported Rhinitis, nasal dryness, (ODB EAP)
(Sanofi- kidneys and to a epistaxis
Aventis), lesser extent in risk of vertebral Blue Cross-
MiacalcinNS the blood and fractures, and pain Flushing, nausea, special
(Novartis) peripheral tissues associated with vomiting, dizziness (all authorization
acute vertebral usually subside (intolerant/failed
fractures spontaneously) etidronate)
NIHB-prior
approval
(intolerant/failed
bisphosphonate
and raloxifene)
CALCIUM/VITAMIN D SUPPLEMENTATION
Calcium 1000-1500 mg Calcium is bone loss absorption of Constipation, flatulence, $8.99/350 tabs
elemental calcium excreted renally. hip BMD & bisphosphonates, phenytoin, gastric distention (generic 500mg
Calcium daily (in divided doses) Unabsorbed fracture risk in tetracyclines, quinolones calcium tablet)
carbonate: 500- calcium is combination with (space apart by >4 hours)
1500mg Note: use calcium excreted in the Vitamin D.6,21 Blue Cross-not a
(elemental citrate if patient on feces benefit
calcium 200mg proton pump inhibitor.
-600mg) NIHB-regular
(needs higher benefit (calcium
pH to be 500mg tab;
absorbed) 20mg/mL liquid;
calcium
Calcium citrate 500mg/vit D
(elemental 400IU tab)
calcium 200-
300mg)
Vitamin D 600-2000 IU/day Extensively calcium absorption Efavirenz may induce Metallic taste, in high $9.97/500 tabs
>2000 IU/day on metabolized by bone loss hepatic catabolism of doses can cause (Vit D 1000 IU
200-1000 IU recommendation of the kidney and hip BMD & fracture 25(OH)D via the CYP450 hypercalcemia or tab)
tablets health care liver. Excreted risk in combination system resulting in vitamin D hypercalciuria $7.99/bottle
400IU/mL liquid professional only primarily in bile. with Calcium.  risk of insufficiency22. In one case, (Vit D 1000
400IU or (option for prescription falls.6 Vitamin D levels were IU/drop)
1000IU drops strength Vitamin D2 decreased to below the limit
50,000 IU 50,000 IU weekly x 8 of detection (18nmol/L) after Blue Cross-not a
capsule (D- weeks to treat low 18 months of treatment23. benefit (except
Forte) vitamin D levels) IFH-400IU tab
Tenofovir use may be regular benefit)
correlated excessive renal
phosphate and calcium NIHB-regular
losses and 1-hydroxylation benefit (drops,
defects of vitamin D24,25 liquid,
400/800/1000 IU
Phenytoin and phenobarbital tablet; 50,000IU
may effects of vitamin D D2 capsule))
Cholestyramine, mineral oil

may absorption of Vitamin
D
Legend: BMD=Bone mineral density; CYP=Cytochrome P450; NSAIDS=Non-steroidal anti-inflammatory drugs; NIHB-Non-Insured Health Benefits (Indian
Affairs); ODB = Ontario Drug Benefit, IFH-Interim Federal Health
Note: Blue Cross- includes AISH. SFI, IFH
References:
1
Guaraldi, G. et al. Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. HIV Clinical Trials. 2004. 5:269-277.
2
Mondy, K. et al. Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infections. Journal of Acquired Immune
Deficiency Syndromes. 2005. 38: 426-431.
3
McComsey, G. et al. Alendronate with calcium and vitamin D supplementation is superior to calcium and vitamin D along in the management of decreased
bone mineral density in HIV. AIDS. 2007. 30: 2473-2482.
4
Huang, J. et al. A double-blinded, randomized controlled trial of zoledronic therapy for HIV-associated osteopenia and osteoporosis. AIDS. 2009. 23: 51-57.
5
Bolland, M. et al. Annual Zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a
randomized control trial. The journal of clinical endocrinology & metabolism. 2007. 92(4): 1283-1288
6
Reid, R. et al. Menopause and osteoporosis Update 2009. SOGC Clinical Practice Guideline. 2009. 31: S1-S47.
7
HIV Insite. Antiretroviral management charts and tables [online]. Available from URL: http://www.hivinsite.com/InSite?page=ar-00-00-02 [Accessed 2010 May
11]
8
Ouellet, D. et al. Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. British Journal of Clinical Pharmacology. 1998.
46:111-6.
9
Sekar, V. et al. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women. Antiviral Therapy.
2008. 13. 563-569
10
Carten, M. et al. Pharmacokinetic interactions between the hormonal emergency contraception, levonorgestrel, and efavirenz. Abstract. 2010. 17th Conference
on Retroviruses and Opportunistic Infections.
11
Mildvan, D. et al. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women.
Journal of the Acquired Immune Deficiency Syndrome. 2002. 29:471-477
12
Crauwels, H. et al. Pharmacokinetic interaction study between TMC278, an NNRTI, and the contraceptives norethindrone plus ethinylestradiol. Abstract. 2009.
12th European AIDS Conference,
13
Kerr, B. et al. Overview of in-vitro and in-vivo drug interaction studies of nelfinavir mesylate, a new HIV-1 protease inhibitor. Abstract. 1997. 4th Conference on
Retroviruses
and Opportunistic Infections.
14
Ouellet, D. et al. Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers. British Journal of Clinical Pharmacology. 1998.
46: 111-116.
15
11]
16
Tackett, D. et al. Atazanavir: a summary of two pharmacokinetic drug interaction studies in healthy volunteers. Abstract. 2003. 10th Conference on
Retroviruses and Opportunistic Infections.
17
Frohlich, M. et al. Oral contraception does not alter single dose saquinavir pharmacokinetics in women. British Journal of Clinical Pharmacology 2004.
57:244-252.
18
11]
19
Brown, K. et al. Drug interactions with new and investigational antiretrovirals. Clinical pharmacokinetics. 2009. 48(4): 211-241
20
Dickinson, L. et al. Pharmacokinetics and drug-drug interactions of antiretrovirals: an update. Antiviral research. 2010. 85: 176-189.
21
Tang, B. et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older:
a meta-analysis. Lancet. 2007. 370: 657-666.
22
Dao, C. et al. Assessment of vitamin D levels among HIV-infected patients in the study to understand the natural history of HIV/AIDS in the era of effective
therapy: SUN study. Abstract. 2010. 17th Conference on Retroviruses and Opportunistic Infections.
23
Gyllensten, K. et al. Severe Vitamin D deficiency diagnosed after introduction of antiretroviral therapy including efavirenz in a patient living at latitude 59N.
AIDS. 2006. 20(14): 1906-1907.
24
Fux, C. et al. Tenofovir use is associated with an increase in serum alkaline phosphatase in the Swiss HIV Cohort Study. Abstract. 2008. 15th Conference on
Retroviruses and Opportunistic Infections.
25
Mueller, C. et al. High prevalence of severe vitamin D deficiency in cART-naïve and successfully treated Swiss HIV patients. Abstract. 2010. 17th Conference
on Retroviruses and Opportunistic Infections.
Amgen Canada Inc. Prolia® product monopgraph April 5, 2011. Available at . http://www.amgen.ca/Prolia_PM.pdf. Accessed June 28, 2011.

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OSTEOPOROSIS MEDICATIONS

Drug Dose Metabolism Efficacy Interactions Side Effects Cost/Coverage

RTV & NFV13 can estrogen

ARVs which may  AUC and

Delavirdine, saquinavir17 and

Please refer to the Oral

Cholestyramine, mineral oil

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