The Effect of High Impact Exercise on Bone and Articular Cartilage in Post-menopausal Women

Osteoarthritis, Knee Clinical Trial

Official title:

The Effect of High Impact Exercise on Bone and Articular Cartilage in Post-menopausal Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03225703
• Other study ID #: R16-P149
• Status: Recruiting
• Phase: N/A
• First received: April 5, 2017
• Last updated: July 18, 2017
• Start date: January 2017
• Est. completion date: January 2019

Study information

• Verified date: July 2017
• Source: Loughborough University
• Contact: Christopher M Hartley, MSC
• Email: c.hartley[@]lboro.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Osteoarthritis (OA) and osteoporosis (OP) affect large numbers of the population. Around 8 million people in the UK are affected by OA and over 300,000 people present with fragility fractures in the UK each year. High impact exercise has been shown to improve markers of bone health but the effect of this exercise on the cartilage is less well understood. A six month, one leg, exercise program based on hopping will be carried out by a group of post-menopausal women. Post-menopausal women are particularly at risk from OP and the research should give information on the feasibility of this type of exercise program in this age group and the effect on cartilage. Participants will be aged between 55 and 70 (at least five years post menopause) with no conditions that would limit their ability to complete the exercise program.

To assess changes in participants' cartilage and bone properties they will be asked to attend several meetings at Loughborough University. Before and after the exercise program participants will have bone density scans and MRI scans of the knee joint. A subset (n=4) will undergo high resolution bone scans that can demonstrate changes in bone structure. The intervention is a home based exercise programme lasting approximately 10 minutes per day. Initially this will be individualised to each participant with the end goal being daily exercise sessions. The programme will last for six months with supervised sessions offered throughout the trial. Using an intervention affecting just one leg will allow the research team to use the other leg as a control.

The research team hypothesise that in a population of post-menopausal women, a six month, unilateral exercise intervention will improve bone mineral density at the proximal femur with no negative effects on articular cartilage.

Description:

The research is a 6 month, intervention study of unilateral (single limb) exercise with the changes in a randomly chosen exercise leg being compared to those in the other (control) leg.

Potential participants (women aged 55-70) will be approached via existing links in the community, at local community centres, through local media, posters and flyers. After initial contact to determine whether they meet the inclusion/exclusion criteria they will be invited to join the study and sent the participant information sheet (PIS). If they then wish to aid in the research they will be invited to a first meeting at Loughborough University.

At the initial meeting the participant can further discuss the project and PIS with the research team. If they fully understand the project and are happy to take part they will be invited to sign the informed consent form. At this stage each participant will be anonymised using a project code. Screening and baseline measurements will then be taken.

Screening questionnaires will be taken following consent to the study. These include a demographic questionnaire, health screen questionnaire, calcium intake questionnaire, physical activity readiness questionnaire (PAR-Q) and bone physical activity questionnaire (BPAQ).

Dual X-ray Absorptiometry (DXA) scans of the whole body, anterior-posterior (AP) spine and dual femur will be taken for each participant to give baseline measurements of bone mineral density.Standard positioning procedures for the measurement being taken will be utilised to allow the calculation of the T-score.

Functional tests will be performed to investigate hopping and balance ability. Unilateral balance will be analysed by measuring postural sway using a force platform. Participants will be asked to balance on one leg for up to 30 seconds. Amplitude of displacement will be calculated, this is the distance between the maximum and minimum centre of pressure (COP) in both directions. COP path length is the total distance travelled and will be calculated and divided by the trial time to give the COP velocity.

Maximal hop height will be measured by recording the vertical displacement of a marker placed on the lumbar spine of each participant whilst conducting a maximal hop. This will be repeated for each leg. The ground reaction force (GRF) of the maximal hop will be recorded using a force platform. Participants will be asked to remain still on the platform for 5 seconds to determine body weight. From this position participants will be asked to lift one leg from the platform and perform a counter movement, maximal hop using their arms to help with propulsion and ensure maximal hop height. After one or two familiarisation attempts the participant will be asked to complete three maximal hops. Allowing for repeats if they do not land fully on the force platform. The peak GRF recorded from these three attempts will be used in the final analysis.

Ground reaction forces during a set of ten hops, which is the end goal of the exercise programme, will be recorded on a force platform. Participants will be asked to remain still on the platform for 5 seconds to determine body weight. From this position participants will be asked to lift one leg from the platform and perform ten counter movement hops using their arms to help with propulsion if able. At the baseline measurements participants will be asked to perform ten hops to the best of their ability, with a rigid support available for them to lean on

A second appointment will be arranged to acquire baseline MRI scans of each knee joint. This will involve the safety checks, conversation with the radiographers and scan times of up to one hour.

Following the MRI scans the exercise leg will be randomly assigned using opaque envelopes. Each envelope will contain a note saying either 'left leg' or 'right leg'. The envelopes will be split into smaller subgroups of eight for minimisation. This will remove the possibility of the first half of volunteers choosing the same leg and removing the randomisation effect on the second half. Participants will be presented with a training diary and instructions on how to complete the exercise programme over six months. The first day of exercise will be completed with the research team at this appointment and the intervention considered started. This second meeting should last for approximately 90 minutes.

The required exercise lasts for no longer than 10 minutes each session and can be performed at home. The intervention will be personalised to the individual's ability and the frequency of the exercise will steadily increase as the participant improves, until the exercise is completed daily. Regular group sessions at Loughborough University will be offered to all participants. The exercise time will remain at ten minutes but the session will be longer, allowing for discussion and check-ups with participants. These will be weekly sessions for the first two months and then once a month for the remaining time.

Follow up measurements will take place six months after the commencement of the exercise programme. Repeat DXA, MRI and functional outcome tests will be carried out on all participants, following the same protocol as at baseline. Again this will occur over two meetings at Loughborough University.

A subset (n=4) will undergo high resolution bone scans (HR-pQCT) that can demonstrate changes in bone structure. This measurement will be taken at the distal tibia and lasts around three minutes per leg. Measurements will be taken pre and post the six month exercise intervention.

Descriptive statistics will be calculated to give information on mean values and variation (standard deviation) of the cohort. This will include age, height, body mass, BMI and time since last menstruation.

Using Levene's test when comparing the exercise to control leg and Mauchly's test of sphericity to compare from baseline to end of study, the variance of the data will be analysed. Normal distribution will be analysed using Shapiro-Wilks test and visual examination of Q-Q plot. If variance is shown to be homogenous and distribution normal within the population then a repeated measures analysis of variance (RM-ANOVA)will be used to detect any significant differences between leg (exercise versus control, time (baseline versus post-intervention) or leg x time interaction in the outcome variable described previously. If any of the outcome measures do not meet the assumptions to conduct parametric tests i.e. ANOVA then Kruskal-Wallis H test will be used to detect any significant change in differences.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: January 2019
• Est. primary completion date: June 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 55 Years to 70 Years

Eligibility

Inclusion Criteria:

• Post-menopausal - at least 12 months since last menstruation and/or hysterectomy, oophorectomy or hormonal contraceptive use

Exclusion Criteria:

• Existing knee, hip or back injury.

• Any medical conditions or injuries which exclude participation in an exercise intervention e.g. heart conditions, hypertension

• BMI > 30 kg/m2

• Participation in a study involving ionising radiation in the previous 12 months.

• Exercise involving ground reaction forces greater than that of jogging more than once a week.

• Contraindications to MRI or DXA

• Osteoporotic (FRAX score requiring the participant is advised to seek treatment)

• Medication affecting bone metabolism or density

Related Conditions & MeSH terms

• BMD
• Osteoarthritis
• Osteoarthritis, Knee
• Osteoporosis
• Osteoporosis, Postmenopausal

Intervention

Behavioral:
• Hopping
A unilateral, hopping based exercise programme lasting six months.

Locations

Country	Name	City	State
United Kingdom	Loughborough University	Loughborough	Leicestershire

Sponsors (1)

Lead Sponsor	Collaborator
Loughborough University

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in T2 Relaxation Time (ms)	T2 mapping is an indicator of the water content in cartilage, with longer relaxation times a marker of cartilage degeneration	6 months (pre and post intervention)
Secondary	Change in Femoral neck bone mineral density (g/cm2)		6 months (pre and post intervention)
Secondary	Change in Femoral neck bone mineral content (g)		6 months (pre and post intervention)
Secondary	Change in Spine bone mineral density (g/cm2)		6 months (pre and post intervention)
Secondary	Change in Spine bone mineral content (g)		6 months (pre and post intervention)
Secondary	Change in Postural sway (mm)		6 months (pre and post intervention)
Secondary	Change in Maximal hop height (mm)		6 months (pre and post intervention)
Secondary	Change in Ground Reaction force Maximal Hop (N)		6 months (pre and post intervention)
Secondary	Change in Ground Reaction force for a set of ten hops (N)		6 months (pre and post intervention)
Secondary	Change in BMD(D100) (mg HA/cm3)	Volumetric Bone mineral density	6 months (pre and post intervention)
Secondary	Change in Total bone mass (mg)		6 months (pre and post intervention)
Secondary	Change in BV/TV (%)	Percent bone volume	6 months (pre and post intervention)
Secondary	Change in pBV/TV (%)	Plate bone volume fraction	6 months (pre and post intervention)
Secondary	Change in rBV/TV (%)	Rod bone volume fraction	6 months (pre and post intervention)
Secondary	Change in pBV/rBV (%)	Plate to - rod ratio	6 months (pre and post intervention)
Secondary	Change in pBV/BV (%)	Plate tissue fraction	6 months (pre and post intervention)
Secondary	Change in rBV/BV (%)	Rod tissue fraction	6 months (pre and post intervention)
Secondary	Change in Bone surface(BS) (mm2)		6 months (pre and post intervention)
Secondary	Change in BS/TV (mm-1)	Bone surface density	6 months (pre and post intervention)
Secondary	Change in Tb.Th (mm)	Trabecular thickness	6 months (pre and post intervention)
Secondary	Change in Tb.Sp (mm)	Trabecular Separation	6 months (pre and post intervention)
Secondary	Change in Tb.N (mm-1)	Trabecular number	6 months (pre and post intervention)
Secondary	Change in Tb.Pf	Trabecular bone pattern (Tb.PF) follows the course of stress lines in the bone. This measurement indicates where the bone is under increased stress.	6 months (pre and post intervention)
Secondary	Change in Conn.D (mm-3)	Connectivity density	6 months (pre and post intervention)
Secondary	Change in DA	Degree of anisotropy	6 months (pre and post intervention)
Secondary	Change in t	Tortuosity (t) is a measure of how well a structure can curve and bend easily. This is an indicator of where the most stress is on the bone structure.	6 months (pre and post intervention)
Secondary	Change in SMI	Structural model index	6 months (pre and post intervention)
Secondary	Change in BRV (mm3)	Bone resorption volume	6 months (pre and post intervention)
Secondary	Change in BFV (mm3)	Bone formation volume	6 months (pre and post intervention)
Secondary	Change in BRM (mg)	Bone resorption mass	6 months (pre and post intervention)
Secondary	Change in BFM (mg)	Bone formation mass	6 months (pre and post intervention)
Secondary	Change in BRF (%)	Bone resorption fraction	6 months (pre and post intervention)
Secondary	Change in BFF(%)	Bone formation fraction	6 months (pre and post intervention)
Secondary	Change in BRR(mm3/week)	Bone resorption rate	6 months (pre and post intervention)
Secondary	Change in BFR(mm3/week)	Bone formation rate	6 months (pre and post intervention)
Secondary	Change in Trabecular orientation distribution (Tb.O.D) (angle in degrees)	This is a measurement of the orientation of the trabeculae in the distal tibia relative to the central axis tibial shaft. The orientation can be categorised into transvers direction and longitudinal direction along the tibial shaft	6 months (pre and post intervention)
Secondary	Change in Ct.Th(mm)	Cortical thickness	6 months (pre and post intervention)
Secondary	Change in B.Po(%)	Bone porosity	6 months (pre and post intervention)
Secondary	Change in Po.Dm(mm)	Pore diameter	6 months (pre and post intervention)
Secondary	Change in Pore volume distribution		6 months (pre and post intervention)
Secondary	Change in Failure load (N)		6 months (pre and post intervention)
Secondary	Change in Strain	This analyses the change in length of the bone over the time period, expressed as % change.	6 months (pre and post intervention)
Secondary	Change in Stiffness (N/mm)		6 months (pre and post intervention)
Secondary	Change in Young's Modulus (GPa)		6 months (pre and post intervention)
Secondary	Change in Mechanical anisotropic ratio		6 months (pre and post intervention)
Secondary	Change in Strain energy density (J/m3)		6 months (pre and post intervention)
Secondary	Change in Strain gradient (µe/mm)		6 months (pre and post intervention)