Musculoskeletal Effects of Bicarbonate
Condition: Muscle Loss; Fractures; Osteoporosis, Age Related; Fall Injury
MeSH terms: Osteoporosis
Intervention: potassium bicarbonate; potassium bicarbonate; Inactive placebo capsule
Intervention description: potassium bicarbonate in dose of 1.0 mmol/kg per day, given in three even daily doses after meals with a full glass of water; potassium bicarbonate in dose of 1.5 mmol/kg per day, given in three even daily doses after meals with a full glass of water; microcrystalline cellulose
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 244.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: potassium bicarbonate; urinary N-telopeptide; urinary nitrogen; net acid excretion

Summary:

      With aging, men and women develop a mild and progressive metabolic acidosis. This occurs as a
      result of declining renal function and ingestion of acid-producing diets. There is extensive
      evidence that severe metabolic acidosis causes bone and muscle loss, but the impact of the
      chronic, mild acidosis on bone and muscle in older individuals has not been established. In a
      recent study, administration of a single dose of bicarbonate daily for 3 months significantly
      reduced urinary excretion of N-telopeptide (NTX), a marker of bone resorption and urinary
      nitrogen, a marker of muscle wasting and improved muscle performance in the women but not the
      men. These and other data support a potential role for bicarbonate as a means of reducing the
      musculoskeletal declines that lead to extensive morbidity and mortality in the elderly.
      Before proceeding to a long-term bicarbonate intervention study, however, it is important to
      identify the dose of bicarbonate most likely to be optimal and to characterize the subjects
      who benefit most from it. This double blind, placebo controlled, dose-finding study will
      evaluate the effects of placebo and two doses of bicarbonate on urinary NTX and nitrogen
      excretion and on lower extremity performance over a 3 month period in 138 men and 138 women,
      age 60 and older. Changes in urinary excretion of NTX and nitrogen and in selected measures
      of lower extremity performance will be compared across the three groups. The safety and
      tolerability of the interventions will also be evaluated. This investigation should provide
      needed information on the appropriate dosing regimen for men and women and on the study
      population that should be enrolled in a future bicarbonate intervention trial to assess the
      long-term effects of this simple, low cost intervention on important clinical outcomes
      including rates of loss in bone and muscle mass, falls, and fractures.
    

Eligibility criteria:

        Inclusion Criteria:

          -  men and women

          -  age 60 and older

          -  community dwelling

          -  women 1 yr since last menses

        Exclusion Criteria:

        Medications:

          1. Oral glucocorticoids for > 10 days in the last 3 months

               -  Cortef (hydrocortisone)

               -  Prednisone

          2. Parenteral glucocorticoids

             • Decadron (dexamethasone)

          3. Osteoporosis medications in the last 6 months

               -  Forteo (teriparatide)

               -  Calcimar, Miacalcin (calcitonin)

               -  Evista (raloxifene)

          4. Osteoporosis medications in the last 2 years

               -  Fosamax (alendronate)

               -  Didronel (etidronate)

               -  Aredia (pamidronate)

               -  Actonel (risedronate)

               -  Reclast (zoledronate)

          5. Tamoxifen in the last 6 months

          6. Calcium/Parathyroid

               -  Rocaltrol (calcitriol)

               -  Zemplar (paricalcitol)

               -  Drisdol, Ergocalciferol

          7. Diuretics currently

               -  hydrocholorothiazide (HCTZ)

               -  Diuril (chlorothiazide)

               -  Thalitone (chlorthalidone)

               -  Zaroxolyn (metolazone)

               -  Dyazide

               -  Maxide

               -  Moduretic

               -  Lasix (forosamine)

               -  Dyrenium (triamterene)

               -  Midamor

          8. Testosterone or estrogen in the last 6 months (vaginal estrogen okay)

          9. Angiotensin converting enzyme (ACE) inhibitors currently

               -  Benazepril (Lotensin)

               -  Captopril (Capoten)

               -  Enalapril (Vasotec)

               -  Fosinopril (Monopril)

               -  Lisinopril (Prinivil, Zestril)

               -  Moexipril (Univasc)

               -  Perindopril (Aceon)

               -  Quinapril (Accupril)

               -  Ramipril (Altace)

               -  Trandolapril (Mavik)

         10. Angiotensin II receptor blockers currently

               -  Candesartan (Atacand)

               -  Eprosartan (Teveten)

               -  Irbesartan (Avapro)

               -  Losartan (Cozaar)

               -  Olmesartan (Benicar)

               -  Telmisartan (Micardis)

               -  Valsartan (Diovan)

        Over-the-Counter Drugs currently

          1. Antacids - any antacid that contains calcium carbonate, aluminum hydroxide, magnesium
             hydroxide, or calcium acetate - selected examples include

               -  TUMS

               -  Mylanta

               -  Maalox

               -  Titralac

               -  Rolaids

               -  Sodium bicarbonate (baking soda)

               -  Note: magaldrate or Riopan® is allowed

          2. Potassium supplements

          3. Salt substitutes

        Conditions/Diseases

          1. renal disease including kidney stones in the past 5 years or glomerular filtration
             rate (GFR) < 60 ml/min/1.73 m2

          2. hyperkalemia (serum potassium >5.3 meq/L; normal range 3.5-5.3 meq/L)

          3. elevated serum bicarbonate (serum bicarbonate > 29 mmol/L; normal range 22-29 mmol/L)

          4. cirrhosis

          5. gastroesophageal reflux disease (GERD) requiring treatment with alkali-containing
             antacids (TUMS, Mylanta, Maalox, Titralac, Rolaids, or sodium bicarbonate)

          6. hyperparathyroidism

          7. untreated thyroid disease

          8. significant immune disorder such as rheumatoid arthritis

          9. current unstable heart disease

         10. active malignancy or cancer therapy in the last year

         11. fasting spot urine calcium/creatinine > 0.38 mmol/mmol after 1 wk off of calcium
             supplements

         12. congestive heart failure, arrhythmias (surgically treated arrhythmias acceptable), or
             myocardial infarction in last 12 months

         13. serum calcium outside the normal range of 8.3-10.2 mg/dl

         14. uncontrolled diabetes mellitus (fasting blood sugar > 130)

         15. alcohol use exceeding 2 drinks/day

         16. peptic ulcers or esophageal stricture

         17. weight <45 or >113.5 kg (<99 or >249.7 lbs)

         18. other abnormalities in screening labs, at discretion of the study physician (the PI)