Vaccines are one of our most effective public health tools but many who need them don't
respond well and are not protected. Adjuvants boost immune responses and are commonly
included in vaccine preparations. Bisphosphonates are the most commonly prescribed treatment
for osteoporosis and may represent a new class of adjuvant. Bisphosphonates are well
tolerated with chronic administration and have very few adverse effects. Research suggests
that these medications can stimulate the immune system.
Bisphosphonates are of special interest in populations with impaired immunity and an
inability to amount protective antibody responses following immunizations. We propose a
pilot study to evaluate the clinical relevance of this finding in humans. We will study the
effect of bisphosphonates on quantitative humoral immune response to hepatitis B vaccine in
healthy older volunteers who have not previously received this vaccine.
Inclusion Criteria:
- Subject willing to undergo hepatitis B vaccination AND be randomized to receive 4
doses of alendronate or placebo
- Age 40-70
- Able to consent for self - ascertained by physician assessment at time of history
and exam.
- Chronic stable medical conditions, if well controlled on current therapies are
allowed. For example individuals with well-controlled angina, hypertension, diabetes
on oral agents, treated or past depression or anxiety, COPD, asthma, metabolic
syndrome, NASH, mild chronic renal insufficiency, past history of malignancy, with no
therapy for at least 5 years may be included.
- Willing to use contraception, if a woman of child-bearing potential (WOCBP)
Exclusion Criteria:
- Pregnant, breastfeeding or planning a pregnancy
- Prior Hepatitis B infection OR vaccination
- Autoimmune disorders of any kind (e. g. multiple sclerosis, rheumatoid arthritis,
lupus, Psoriasis etc.)
- HIV or Hepatitis C seropositive
- Any known immunodeficiency (decompensated cirrhosis, HIV/AIDS, prior bone marrow
transplant, or other known immunodeficiency)
- Patients on any immunosuppressive agents including systemic corticosteroids,
calcineurin inhibitors, mTOR inhibitors, lymphocyte depleting biologic agents,
anti-TNF agents, and others; chemotherapeutic anti-neoplastic agents within 5 years.
Stable doses of inhaled corticosteroids for asthma/COPD are allowed.
- Gastroesophageal reflux disease (GERD), peptic ulcer disease, chronic proton pump
inhibitors, chronic antacid use
- Chronic non-steroidal anti-inflammatory use; daily ASA for cardiac prophylaxis is
allowed.
- Esophageal disorders of any kind
- Recent major dental work in the preceding 6 months, excluding dental cleaning and
simple cavity filling
- History of jaw trauma
- Current or prior bisphosphonate use
- Prior history of severe reactions to vaccines
- Yeast or bisphosphonate allergy
- History of hypocalcemia
- Inability to stand or sit upright for at least 30 minutes.
- Any malabsorptive disorder including celiac disease, CF, Inflammatory bowel disease,
recurrent C. difficile colitis, other colitis, prior gastrectomy, bariatric surgery
or chronic diarrhea.
- Diabetes requiring insulin
- Body mass index > 31
