Hip Fracture
Conditions
Keywords
Hip fracture, Nutritional supplement, Bisphosphonates, Bone mineral density, Body composition
Brief summary
The study hypothesis is that nutritional supplementation together with bisphosphonates have a better preserving effect on bone mineral density (BMD) after hip fracture than bisphosphonates alone and that nutritional supplementation given postoperatively for 6 months preserve lean body mass in elderly hip fracture patients.
Detailed description
Inclusion criteria: Men and women, ≥ 60 years of age with a recent fracture of the femoral neck or trochanter, admitted to any of the four University hospitals in Stockholm, Sweden. Patients are randomized into three groups by sealed enveloped technique in blocks by 12, thus assuring that each center had an equal distribution of patients in the three treatment groups. Patients randomly assigned and followed for 12 months. Each center with a doctor in charge and a trial nurse. The trial nurse in collaboration with the doctor are responsible of the randomization procedure and that blood samples are taken in the morning of the first weekday after inclusion at the ward and further that the dual-energy X-ray (DXA) and all estimates are done during hospital stay.The pharmacological treatment and nutritional supplementation starts as soon as the patients are circulatory stable, able to take food by mouth and are able to sit in an upright position one hour after taking the tablets.Patients are examined at baseline with a follow up at 6 and 12 months.
Interventions
DRUGRisedronate
The bisphosphonate group (B) receive 35 mg risedronate (Optinate® Septimum) once weekly for 12 months and calcium (1000 mg) and vitamin D3 (800 IU) (Calcichew-D3®) daily for 12 months.
OTHERNutritional supplement
The bisphosphonate and nutritional supplemented group (BN) receive 35 mg risedronate once weekly for 12 months plus nutritional supplement (Fresubin® protein energy drink) during the first six months following hip fracture and also calcium (1000 mg) and vitamin D3 (800 IU) daily for 12 months.
DIETARY_SUPPLEMENTCalcium and vitamin D3
The patients in the control group (C) receive orally administered calcium 1000 mg and 800 IU vitamin D3 (Calcichew-D3®) daily for 12 months.
Sponsors
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 60 years * Recent fracture of the femoral neck or trochanter * Without severe cognitive impairment * Ambulant before fracture * BMI ≤ 28
Exclusion criteria
* Abnormal parameters regarding liver i.e. S-Alanine aminotransferase (S-ALAT) and S-Aspartate aminotransferase (S-ASAT) ≥ twice as normal * Abnormal parameters regarding kidney i.e. S-Creatinine \> 130 µg/L * Primary hyperparathyroidism, osteogenesis imperfecta, Paget´s disease * Myeloma * Lactose intolerance * Dysphagia * Esophagitis * Gastric ulcer * Malignancy * Diabetes with nephropathy or retinopathy * Active iritis or uveitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | Baseline, 6 months and 12 months | Total hip bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The DXA image is two dimensional and BMD was expressed as areal density, grams per square centimeter (g/cm\^2). The change in BMD between baseline, 6 and 12 months was registered. |
| Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | Baseline, 6 months and 12 months | Total body mineral density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA). The DXA image is two dimensional and BMD was expressed as areal density, grams per square centimeter (g/cm\^2). The change in BMD between baseline, 6 and 12 months was registered. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | Baseline, 6 and 12 months | Total body composition, including lean mass composed of muscle, visceral organs and water (LM), fat mass (FM) and bone mineral content (BMC) was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at 6 and 12 months follow up. The sum of lean mass (LM) and BMC represents fat-free mass (FFM). To normalize for body size, FFM was divided by height squared to calculate fat-free mass index (FFMI, kg/m\^2). |
| Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | Baseline, 6 and 12 months | Total body composition, including lean mass composed of muscle, visceral organs and water (LM), fat mass (FM) and bone mineral content (BMC) was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at 6 and 12 months follow up.To normalize for body size, FM was divided by height squared to calculate fat mass index (FMI, kg/m\^2). |
Countries
Sweden
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group B, Bisphosphonate Patients were randomized to treatment with bisphosphonates (risedronate 35 mg weekly for 12 months. All patients received calcium (1,000 mg) and vitamin D3 (800 IU) daily. | 28 |
| Group BN/N, Bisphosphonates Along With Nutritional Supplementation Patients allocated to intervention BN/N received 35 mg risedronate once weekly for 12 months plus a nutritional supplement (Fresubin protein energy drink) during the first 6 months after hip fracture. The supplement contained 150 kcal and 10 g protein/100 mL milk-based protein (80 % casein and 20 % whey). Patients were prescribed 200 mL twice daily, totaling 600 kcal with 40 g protein. | 26 |
| C, Control Patients allocated to group C served as controls and received 1,000 mg Calcium and 800 IU vitamin D3 daily for 12 months. | 25 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 8 | 1 |
Baseline characteristics
| Characteristic | Group BN/N, Bisphosphonates Along With Nutritional Supplementation | C, Control | Total | Group B, Bisphosphonate |
|---|---|---|---|---|
| Age, Continuous | 82 Years | 75 Years | 81 Years | 82 Years |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment Sweden | 26 participants | 25 participants | 79 participants | 28 participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 56 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 23 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 2 / 28 | 0 / 26 | 3 / 25 |
| serious Total, serious adverse events | 0 / 28 | 0 / 26 | 0 / 25 |
Outcome results
Primary
Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture.
Total body mineral density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA). The DXA image is two dimensional and BMD was expressed as areal density, grams per square centimeter (g/cm\^2). The change in BMD between baseline, 6 and 12 months was registered.
Time frame: Baseline, 6 months and 12 months
Population: Seventy-nine patients were initially included in the study, of whom 67 were available at final follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B, Bisphosphonate | Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow-up at 6 months | -0.005 g/cm^2 | Standard Deviation 0.018 |
| B, Bisphosphonate | Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow-up at 12 months | -0.003 g/cm^2 | Standard Deviation 0.022 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow-up at 6 months | -0.006 g/cm^2 | Standard Deviation 0.018 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow-up at 12 months | 0.0006 g/cm^2 | Standard Deviation 0.019 |
| C, Control | Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow-up at 6 months | -0.012 g/cm^2 | Standard Deviation 0.019 |
| C, Control | Total Body Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow-up at 12 months | -0.017 g/cm^2 | Standard Deviation 0.02 |
p-value: 0.05ANCOVA
Primary
Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture.
Total hip bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). The DXA image is two dimensional and BMD was expressed as areal density, grams per square centimeter (g/cm\^2). The change in BMD between baseline, 6 and 12 months was registered.
Time frame: Baseline, 6 months and 12 months
Population: Seventy-nine patients were initially included in the study, of whom 67 were available at final follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B, Bisphosphonate | Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.008 g/cm^2 | Standard Deviation 0.037 |
| B, Bisphosphonate | Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.012 g/cm^2 | Standard Deviation 0.042 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | 0.005 g/cm^2 | Standard Deviation 0.026 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.004 g/cm^2 | Standard Deviation 0.025 |
| C, Control | Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.017 g/cm^2 | Standard Deviation 0.026 |
| C, Control | Total Hip Bone Mineral Density (BMD) at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.018 g/cm^2 | Standard Deviation 0.032 |
p-value: 0.05ANCOVA
Secondary
Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture.
Total body composition, including lean mass composed of muscle, visceral organs and water (LM), fat mass (FM) and bone mineral content (BMC) was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at 6 and 12 months follow up.To normalize for body size, FM was divided by height squared to calculate fat mass index (FMI, kg/m\^2).
Time frame: Baseline, 6 and 12 months
Population: Seventy-nine patients were initially included in the study, of whom 67 were available at final follow-up. Calculations revealed that a sample size of 40 patients per group was required to detect a difference in lean mass between groups (power = 80 %, a = 0.05). However, the study was closed after 4 years due to difficulties in recruiting patients and the study was switched to an exploratory design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B, Bisphosphonate | Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.6 kg/m^2 | Standard Deviation 1.4 |
| B, Bisphosphonate | Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.3 kg/m^2 | Standard Deviation 1.6 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | 0.1 kg/m^2 | Standard Deviation 0.8 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | 0.1 kg/m^2 | Standard Deviation 0.8 |
| C, Control | Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.1 kg/m^2 | Standard Deviation 0.8 |
| C, Control | Body Composition, Including Fat Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.1 kg/m^2 | Standard Deviation 1.1 |
Secondary
Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture.
Total body composition, including lean mass composed of muscle, visceral organs and water (LM), fat mass (FM) and bone mineral content (BMC) was measured by dual-energy X-ray absorptiometry (DXA) at baseline and at 6 and 12 months follow up. The sum of lean mass (LM) and BMC represents fat-free mass (FFM). To normalize for body size, FFM was divided by height squared to calculate fat-free mass index (FFMI, kg/m\^2).
Time frame: Baseline, 6 and 12 months
Population: Seventy-nine patients were initially included in the study, of whom 67 were available at final follow-up. Calculations revealed that a sample size of 40 patients per group was required to detect a difference in lean mass between groups (power = 80 %, a = 0.05). However, the study was closed after 4 years due to difficulties in recruiting patients and the study was switched to an exploratory design.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| B, Bisphosphonate | Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.4 kg/m^2 | Standard Deviation 1.2 |
| B, Bisphosphonate | Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.5 kg/m^2 | Standard Deviation 1.2 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.9 kg/m^2 | Standard Deviation 0.7 |
| BN/N, Bisphosphonate Along With Nutritional Supplementation | Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.8 kg/m^2 | Standard Deviation 0.9 |
| C, Control | Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 6 months | -0.4 kg/m^2 | Standard Deviation 0.8 |
| C, Control | Body Composition, Including Lean Mass at Baseline, 6 and 12 Months After Hip Fracture. | follow up at 12 months | -0.5 kg/m^2 | Standard Deviation 0.8 |
p-value: 0.05ANCOVA