Osteopenia, Bone Disease, Metabolic
Conditions
Keywords
potassium citrate
Brief summary
The purpose of this study is to investigate whether the use of alkali compounds, i.e. potassium citrate (K3C6H5O7, hereinafter KCitr) is effective in preventing the progression of osteopenia. A randomized clinical trial (RCT, placebo-controlled, double-blind) has been planned to evaluate the effect of the daily administration of KCitr (3 g/die, K 30 mEq). The efficacy will be evaluated by comparing the circulating levels of bone turnover markers at the baseline and after the treatment (3, 6 months).
Detailed description
Bone tissue carries out some of the important metabolic functions, including the regulation of acid-base balance. In order to buffer the systemic acidosis, the skeleton acts as a ion exchange column modifying the composition of the mineral portion, i.e. the hydroxyapatite. There is a linear correlation between elimination of calcium and acidosis: the higher is the acidosis, the higher will be the loss of calcium from bones. In vitro experiments showed that acidosis also directly influences the cellular component of bone by increasing the osteoclast activity and inhibiting the production of the mineralized matrix by osteoblast. Since the low pH is a risk factor that accelerates the bone loss, the use of alkalizing compounds could prevent the osteopenia or support the conventional therapy of the osteoporosis. KCitr is an alkaline compound which may be used in metabolic acidosis. Potassium is an alkaline metal that plays a pivotal role in the function of all living cells. Citric acid is a key molecule of the Krebs cycle, and it is abundant in bone where exhibits a stabilizing function. Although clinical data regarding the KCitr effectiveness on calcium metabolism are encouraging, it is still unclear whether the beneficial effects are due exclusively to the buffering function or whether KCitr may affect the bone cells activity. The purpose of this study is to evaluate the effects of KCitr on bone metabolism. We hypothesize that administration of potassium citrate to postmenopausal women with osteopenia will delay (or will prevent) the weakening of bone mass. Postmenopausal women with osteopenia (T score between -1.0 and -2.5) and no history of fracture will be randomized to assume KCitr ate or placebo, daily for six months. Primary outcomes will be evaluated by measuring markers of bone turnover, which will be measured at baseline (before treatment), in the mid-term (3 months) and at the end (6 months).
Interventions
DIETARY_SUPPLEMENTPlacebo
Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
DIETARY_SUPPLEMENTVitamin D3
400 IU/die Vitamin D3 daily by mouth
DIETARY_SUPPLEMENTCalcium carbonate
500 mg/die calcium carbonate daily by mouth
DIETARY_SUPPLEMENTPotassium citrate
Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
Sponsors
Istituto Ortopedico Rizzoli
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women, more than 5 years post menopause * Osteopenia (T-score \< -1 and \> -2.5) * Low risk of fracture (FRAX: \< 20 major osteoporotic; \< 3 hip fracture)
Exclusion criteria
* Hyperkalemia * Renal insufficiency * Nephrolithiasis * Use of potassium sparing diuretics * Use of potassium supplements * Use of therapies influencing bone metabolism (e.g. corticosteroids, thiazide diuretics, aromatase inhibitors, estrogens) * Use of protonic pump inhibitors * Current or recent use of bisphosphonates (stopped less than three years prior to the start of the study) * Gastrointestinal disorders that hamper nutrient absorption; * Mental or psychiatric disorders that preclude the possibility of correctly adhering to the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0), 3 months (T3) 6 months (T6) | Carboxyterminal cross-linked telopeptide of type I collagen (CTX) is a degradation product of the type I collagen; it is considered as a marker of bone resorption. The concentration of CTX (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05. |
| Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0), 3 months (T3) 6 months (T6) | Tartrate-resistant acid phosphatase 5b isoenzyme (TRAcP5b) is a specific product of osteoclasts; it is considered as a marker of bone resorption. The concentration of TRAcP5B (U/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium Citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05. |
| Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0), 3 months (T3) 6 months (T6) | N-terminal propeptide of type I procollagen (P1NP) is a product of the conversion of procollagen to collagen; it is considered as a marker of bone formation. The concentration of P1NP (pg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05. |
| Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0), 3 months (T3) 6 months (T6) | Bone-specific alkaline phosphatase (BAP) is a specific product of osteoblasts; it is considered as a marker of bone formation. The concentration of BAP (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05. |
Countries
Italy
Participant flow
Recruitment details
Participants were recruited among the cohort of post-menopausal women attending to the Radiodiagnostic Unit of Istituto Ortopedico Rizzoli (IOR) from September 2015 to February 2017 to perform the periodic measurements of lumbar (at L2-L4 level) and femoral bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA).
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group, Potassium Citrate Potassium citrate Calcium carbonate Vitamin D3
Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
Vitamin D3: 400 IU/die Vitamin D3 daily by mouth
Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | 20 |
| Control Group, Placebo Placebo (Excipients) Calcium carbonate Vitamin D3
Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
Vitamin D3: 400 IU/die Vitamin D3 daily by mouth
Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Control Group, Placebo | Total | Treatment Group, Potassium Citrate |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 4.95 | 59.5 years STANDARD_DEVIATION 4.93 | 60.8 years STANDARD_DEVIATION 4.67 |
| Body mass index (BMI) | 22.9 kg/m^2 STANDARD_DEVIATION 3.8 | 23.3 kg/m^2 STANDARD_DEVIATION 4.1 | 23.6 kg/m^2 STANDARD_DEVIATION 4.4 |
| Citrate (24h urine) | 3.50 mmol day-1 STANDARD_DEVIATION 1.74 | 3.24 mmol day-1 STANDARD_DEVIATION 1.71 | 2.97 mmol day-1 STANDARD_DEVIATION 1.68 |
| Citrate (fasting-morning urine) | 3.40 mol mol-1 STANDARD_DEVIATION 2.39 | 3.09 mol mol-1 STANDARD_DEVIATION 1.96 | 2.77 mol mol-1 STANDARD_DEVIATION 1.39 |
| Major osteoporotic risk | 4.8 % (percentage probability) STANDARD_DEVIATION 1.5 | 5.2 % (percentage probability) STANDARD_DEVIATION 2.6 | 5.7 % (percentage probability) STANDARD_DEVIATION 3.4 |
| Minor osteoporotic risk | 1.0 % (percentage probability) STANDARD_DEVIATION 0.5 | 1.0 % (percentage probability) STANDARD_DEVIATION 0.6 | 1.1 % (percentage probability) STANDARD_DEVIATION 0.8 |
| pH (24h urine) | 6.03 pH value | 6.08 pH value | 6.13 pH value |
| pH (fasting-morning urine) | 5.87 pH value | 6.00 pH value | 6.13 pH value |
| Potassium (24h urine) | 30.40 milliequivalent day-1 STANDARD_DEVIATION 12.98 | 29.50 milliequivalent day-1 STANDARD_DEVIATION 13.85 | 28.60 milliequivalent day-1 STANDARD_DEVIATION 14.97 |
| Race/Ethnicity, Customized Caucasian | 20 Participants | 40 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 40 Participants | 20 Participants |
| Region of Enrollment Italy | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| T score (BMD femural neck) | -1.7 scores on a scale STANDARD_DEVIATION 0.5 | -1.6 scores on a scale STANDARD_DEVIATION 0.5 | -1.6 scores on a scale STANDARD_DEVIATION 0.4 |
| T score (L2 - L4) | -1.4 scores on a scale STANDARD_DEVIATION 0.6 | -1.6 scores on a scale STANDARD_DEVIATION 0.6 | -1.7 scores on a scale STANDARD_DEVIATION 0.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 1 / 20 | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months.
Carboxyterminal cross-linked telopeptide of type I collagen (CTX) is a degradation product of the type I collagen; it is considered as a marker of bone resorption. The concentration of CTX (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05.
Time frame: Baseline (T0), 3 months (T3) 6 months (T6)
Population: 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty).~2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group, Potassium Citrate | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 0.53 µg/L | Standard Error 0.08 |
| Treatment Group, Potassium Citrate | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 0.64 µg/L | Standard Error 0.08 |
| Treatment Group, Potassium Citrate | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 0.63 µg/L | Standard Error 0.08 |
| Control Group, Placebo | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 0.64 µg/L | Standard Error 0.05 |
| Control Group, Placebo | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 0.56 µg/L | Standard Error 0.05 |
| Control Group, Placebo | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 0.54 µg/L | Standard Error 0.06 |
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0p-value: 0.172t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0p-value: 0.027t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3p-value: 0.053t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0p-value: 0.002t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T6 vs T0p-value: 0.006t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T6 vs T3p-value: 0.139t-test, 1 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0p-value: 0.967t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3p-value: 0.446t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6p-value: 0.869t-test, 2 sided
Primary
Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months.
Bone-specific alkaline phosphatase (BAP) is a specific product of osteoblasts; it is considered as a marker of bone formation. The concentration of BAP (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05.
Time frame: Baseline (T0), 3 months (T3) 6 months (T6)
Population: 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty).~2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group, Potassium Citrate | Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 21.89 µg/L | Standard Error 1.67 |
| Treatment Group, Potassium Citrate | Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 19.81 µg/L | Standard Error 1.67 |
| Treatment Group, Potassium Citrate | Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 16.83 µg/L | Standard Error 1.37 |
| Control Group, Placebo | Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 20.36 µg/L | Standard Error 1.17 |
| Control Group, Placebo | Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 18.27 µg/L | Standard Error 1 |
| Control Group, Placebo | Changes in Serum Levels of Bone-specific Alkaline Phosphatase (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 15.79 µg/L | Standard Error 1.09 |
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0p-value: 0.094t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0p-value: 0.0004t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3p-value: 0.008t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0p-value: 0.002t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0p-value: <0.0001t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3p-value: 0.0007t-test, 1 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0p-value: 0.458t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3p-value: 0.434t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6p-value: 0.555t-test, 2 sided
Primary
Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months.
N-terminal propeptide of type I procollagen (P1NP) is a product of the conversion of procollagen to collagen; it is considered as a marker of bone formation. The concentration of P1NP (pg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05.
Time frame: Baseline (T0), 3 months (T3) 6 months (T6)
Population: 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty).~2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group, Potassium Citrate | Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 17.45 pg/L | Standard Error 1.48 |
| Treatment Group, Potassium Citrate | Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 16.24 pg/L | Standard Error 1.6 |
| Treatment Group, Potassium Citrate | Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 14.97 pg/L | Standard Error 1.51 |
| Control Group, Placebo | Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 18.82 pg/L | Standard Error 1.73 |
| Control Group, Placebo | Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 18.39 pg/L | Standard Error 1.75 |
| Control Group, Placebo | Changes in Serum Levels of N-terminal Propeptide of Type I Procollagen (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 16.77 pg/L | Standard Error 1.89 |
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0p-value: 0.213t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0p-value: 0.191t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3p-value: 0.234t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0p-value: 0.37t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T6 vs T0p-value: 0.176t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T6 vs T3p-value: 0.139t-test, 1 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0p-value: 0.551t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3p-value: 0.371t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6p-value: 0.466t-test, 2 sided
Primary
Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months.
Tartrate-resistant acid phosphatase 5b isoenzyme (TRAcP5b) is a specific product of osteoclasts; it is considered as a marker of bone resorption. The concentration of TRAcP5B (U/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium Citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis). Differences will be considered to be statistically significant for p-value \<0.05.
Time frame: Baseline (T0), 3 months (T3) 6 months (T6)
Population: 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty).~2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group, Potassium Citrate | Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 2.69 U/L | Standard Error 0.29 |
| Treatment Group, Potassium Citrate | Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 2.35 U/L | Standard Error 0.2 |
| Treatment Group, Potassium Citrate | Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 2.79 U/L | Standard Error 0.27 |
| Control Group, Placebo | Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | Baseline (T0) | 2.64 U/L | Standard Error 0.22 |
| Control Group, Placebo | Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | 3 months (T3) | 2.85 U/L | Standard Error 0.22 |
| Control Group, Placebo | Changes in Serum Levels of Tartrate-resistant Acid Phosphatase 5b Isoenzyme (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. | 6 months (T6) | 2.25 U/L | Standard Error 0.14 |
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0p-value: 0.954t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0p-value: 0.798t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3p-value: 0.377t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0p-value: 0.886t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T6 vs T0p-value: 0.04t-test, 1 sided
Comparison: Paired analysis within the group to evaluate the effect of Placebo: T6 vs T3p-value: 0.017t-test, 1 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0p-value: 0.343t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3p-value: 0.859t-test, 2 sided
Comparison: Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6p-value: 0.172t-test, 2 sided