Efficacy And Security Of Annual And Biennial Zoledronic Acid For Osteoporosis Treatment In An HIV-Infected Patients' Cohort

Study Overview
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Brief Summary
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The purpose of this project is to determine the incidence of osteoporosis in the investigators' population of HIV-infected patients and to assess the efficacy and security of zoledronic acid, whose efficacy in post-menopausal women with high fracture risk treatment and in Paget's disease treatment has already been demonstrated.

Detailed Description
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The lower bone mineral density that has been described in patients with HIV-infection has not meant an increase of long term complications. Nevertheless, it could involve an increase if the associated co-morbidity in the future, taking in care that in general population osteoporosis increases 4 times the pathologic fracture risk. That is why it is necessary to know the real prevalence of osteoporosis in this population of patients so the real dimensions of the problems can be defined. This project wills to determine the incidence of osteoporosis in our population of HIV-infected patients and to assess the efficacy and security of zoledronic acid. If the annual use of endovenous zoledronic acid obtains equivalent results to those obtained with oral and weekly alendronate in other studies with the same population, its use would be justified because of its posology benefits. The annual administration can improve compliance in patients who are receiving a big quantity of drugs, as HIV-infected patients do, and who probably have to be treated for life. Moreover, its elimination is renal so there is absence of interactions with antiretroviral drugs what makes of zoledronic acid a very promising alternative. Finally, there is no risk of digestive intolerance because of its parenteral administration and it has a better posology than oral bisphosphonates.

Official Title
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Efficacy and Security of Annual and Biennial Zoledronic Acid for Osteoporosis Treatment in an HIV-infected Patients' Cohort

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Zoledronic acid
* Behavioral: Lifestyle modifications
* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old or older. Documented HIV-1 infection, with or without antiretroviral treatment. Presence of WHO osteoporosis criteria, defined as t-score under -2.5 in lumbar, hip and/or trochanter (DEXA in the last 6 months is needed). Willing to follow the study protocol. Informed Consent signature. Exclusion Criteria: In women, pregnancy or breastfeeding. Other possible causes of secondary osteoporosis. Creatinine over 2.3 mg/mL. Glomerular filter less than 50 mL/min (estimated through MDRD). Treatment for Osteoporosis in the last 4 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1-ANNUAL<br>1. Zoledronic acid + Lifestyle modifications (experimental) | Drug: Zoledronic acid<br>* Zoledronic Acid 5mg/year<br>Behavioral: Lifestyle modifications<br>* Lifestyle modifications<br>|
| Other: 2-CONTROL<br>2. Lifestyle modifications (control) | Behavioral: Lifestyle modifications<br>* Lifestyle modifications<br>|
| Experimental: 3-BIENNIAL<br>3. Zoledronic acid + Lifestyle modifications (experimental) | Behavioral: Lifestyle modifications<br>* Lifestyle modifications<br>Drug: Zoledronic acid<br>* Zoledronic acid (5mg/2years)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Increase in lumbar (L2-4) and femoral (trochanter, femur neck, total femur and hip) t-score bone mineral density |  | Evolution from baseline to week 48 | 
| Increase in lumbar (L2-4) and femoral (trochanter, femur neck, total femur and hip) t-score bone mineral density |  | Evolution from baseline to week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | From baseline to week 96 | 
| Lab tests |  | Evolution from baseline to week 96 | 
| Related clinical events (bone fractures) |  | From baseline to week 96 | 
| Osteoblastic/Osteoclastic activity, bone formation/reabsorption. |  | Evolution from baseline to week 48 | 
| Osteoblastic/Osteoclastic activity, bone formation/reabsorption. |  | Evolution from baseline to week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, HIV infection, Bisphosphonates, Zoledronic acid