The Effects of Potassium Citrate on Bone Metabolism
Condition: Bone Diseases, Metabolic; Osteoporosis, Postmenopausal
MeSH terms: Osteoporosis; Bone Diseases; Osteoporosis, Postmenopausal; Bone Diseases, Metabolic; Metabolic Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      Skeletal buffering of chronic acid loads may contribute to a significant amount of bone loss
      over time. Evidence from a few small short-term studies suggests that basic compounds, namely
      potassium citrate and potassium bicarbonate may reduce bone loss and improve bone density.

      The purpose of this study is to evaluate the effects of potassium citrate on bone metabolism.
      We hypothesize that administration of potassium citrate to postmenopausal women with
      osteopenia will reduce bone resorption and improve bone mineral density.

      Postmenopausal women with osteopenia (T score between -1.0 and -2.5) and no history of
      fracture will be randomized to either daily potassium citrate or placebo for one year.
      Primary outcomes will be markers of bone turnover, which will be measured over 12 months.
      Secondary outcomes will be bone mineral density, compliance, and adverse events.
    

Detailed description: 
      Participants were recruited from a single academic center. Subjects underwent screening at
      the Clinical Translational Science Center (CTSC) at Weill Cornell Medical College (WCMC).
      Study visits occurred at the CTSC where investigators administered and monitored
      questionnaires, compliance, adverse events, and endpoint measurements. Subjects were assigned
      an anonymous study number at the beginning of the trial, which was used to track the
      participant's data throughout the study. The protocol was approved by the Institutional
      Review Board (IRB) and the procedures followed were in accordance with the ethical standards
      of the IRB and the CTSC. All patients provided informed consent.

      Treatment Groups Participants were assigned to either the treatment or placebo group using a
      randomization schema generated by the statistician. The randomization method was blocked
      randomization with a blocking factor of 4. The blocked randomization was not stratified by
      any other factors. The study was conducted in a double blind manner. The study medication,
      K-citrate, or placebo, was dispensed through the New York Presbyterian Hospital (NYPH)
      pharmacy. Bottles in the pharmacy were sequentially numbered and the number was linked to the
      blocked randomization scheme. Only the statistician and the pharmacist knew the meaning of
      the numbered codes and only the statistician knew the blocking assignment. Blocked
      randomization with balanced randomization of each block and blocks of the same size was
      performed by the RANDOM procedure within the WinPepi Version 11.1.

      Investigators who administered questionnaires and assessed compliance, adverse effects or
      endpoint information were blind to group assignment. Only study investigators were able to
      enroll participants in the study and assign them to treatment arms. Those assigned to the
      treatment group received the study drug (40 mEq daily K Citrate: two 10 mEq tablets twice
      daily); those assigned to the control group received inert tablets of the same quantity. All
      participants received daily supplementation with Citracal (630 mg calcium citrate and 400 IU
      vitamin D3 per two caplets). All supplements and medications were provided by Mission
      Pharmacal/Bayer Pharmaceuticals in Boerne, Texas. Subjects discontinued their prior
      supplements at the time of entry to the study and were advised to adhere to the standardized
      supplementation regimen outlined by the protocol.

      Measurements and Outcomes Subjects were evaluated at baseline, 1, 3, 6, and 12 months. The
      following outcomes were measured: change in bone turnover markers including u-NTX, BSAP, OC
      and P1NP; changes in 24 hour urinary concentrations of citrate, sulfate, and calcium; and
      changes in BMD measured from baseline to 12 months. Adverse events and compliance were
      measured at each visit over the study duration. Adverse events pertained to medication side
      effects, including, but not limited to, gastrointestinal complaints, nausea, diarrhea, and
      stomach pain, as well as the development of hyperkalemia or metabolic acidosis. If any of the
      following occurred, potassium exceeded 5.2 mmol/L; bicarbonate level exceeded 32 mmol/L;
      creatinine increased by more than 30% or rose above 2.0 ng/dL; or GFR was < 60, study
      medications were stopped until the parameter normalized, at which point the medication was
      resumed at half dose: Compliance was assessed by remaining pill count; good compliance was
      defined at ≤ 20% of pills remaining, or ≤ 18 pills remaining for each 3-month dose
      allocation.

      Baseline measurements included dietary assessment (block food frequency questionnaire) and
      blood pressure. Laboratory evaluation was performed at the General Core Laboratory at WCMC
      and included a basic metabolic panel, calcium, albumin and thyroid stimulating hormone (TSH).
      25-OH and 1,25(OH)2 Vitamin D were measured by radioimmunoassay (Immunodiagnostic Systems,
      Scottsdale, Arizona). The interassay coefficient of variation (CV) was <8.2% and <13%,
      respectively. Intact parathyroid hormone (i-PTH) was measured by immunoradiometric assay
      (Scantibodies Laboratories, Santee, California; CV <6.4%). Markers of bone turnover included
      osteocalcin (OC: quantitative immunoradiometric assay, DiaSorin, Stillwater, Minnesota; CV
      <9.5%) , bone specific alkaline phosphatase (BSAP: solid phase monoclonal antibody
      immunoenzymetric assay, Immunodiagnostics Systems, Scottsdale, Arizona; CV<6.4%), procollagen
      type 1 amino-terminal propeptide (P1NP: quantitative radioimmunoassay, Orion Diagnostica,
      Espoo, Finland; CV<9.8%), urinary N-telopeptide (U-NTX: quantitative enzyme-linked
      immunosorbent assay kit, Wampole Laboratories INC Princeton, New Jersey; CV<5.0%). All
      specimens were collected as fasting morning samples. The urinary-NTX was a second morning
      void. The specimens were frozen and batch analyzed. 24 hour urinary collections for calcium,
      creatinine, sulfate, citrate and sodium were analyzed at Quest Diagnostics. BMD was performed
      at lumbar spine, total hip and femoral neck using dual-energy X-ray Absorptiometry (DXA)
      Hologic; Bedford, Massachusetts. The least significant change (LSC) for the DXA was 0.025 at
      the lumbar spine, 0.025 at the femoral neck and 0.015 at the radius. Two technologists, both
      certified by the International Society for Clinical Densitometry, performed all DXA testing
      on the participants.
    

Intervention name(s): potassium citrate
Intervention type(s): Drug
Intervention description(s): 20 meq by mouth in capsule form twice daily
Other intervention name(s): uro cit
Intervention MeSH terms: Potassium Citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double Blind Placebo Controlled Trial
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: postmenopausal osteopenia; treatment; bone loss