Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 1 Bisphosphonates: Overview Adrian D. LeBlanc Rev. Dec. 18, 2007

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 2 Class Objectives Crewmember will have a basic understanding of the problem of bone loss in space and the need for an effective countermeasure. Crewmember will understand the two dosing options and know which one he/she has selected. Crewmember will understand what testing will be conducted pre-, in- and postflight. Crewmember will understand the risks (and risk mitigation) associated with this study.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 3

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 4

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 5 Rationale and Hypothesis Reducing bone loss, fracture risk and renal stones on ISS and other long-duration missions envisioned for the Constellation Program (Lunar Outpost, Mars, etc.) are a NASA goal. To date, in-flight exercise regimens or nutritional modification alone have not prevented bone loss in cosmonauts and astronauts on long-duration flights. Studies show that the primary cause of the spaceflight bone loss and resultant renal stone risk is increased bone resorption. Bisphosphonates are used clinically for prevention and treatment of osteoporosis in young and older individuals by reducing bone resorption. Bisphosphonates, alendronate (oral) and zoledronic acid (I.V.), have been shown to inhibit resorption and decrease bone loss, fracture risk and renal stone risk in ground-based disuse studies. Study Hypothesis: The combined effect of bisphosphonates plus the standard in- flight exercise regimen will have a measurable effect versus exercise alone in preventing spaceflight induced bone loss and renal stones.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 6 Dosing Overview Alendronate: taken as a 70-mg tablet once a week before and during flight, starting 17 days before launch OR Zoledronic Acid: 4 mg dose given once by 20 minute I.V. infusion 45 days before launch

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 7 Experiment Measurements Determine the effectiveness of bisphosphonate treatment (either oral alendronate or I.V. zoledronic acid) in preventing space flight induced bone loss and renal stones as determined by: Bone Loss Hip BMD as measured by QCT Whole body and regional BMD by DXA Lower leg BMD by pQCT Serum and urine markers of bone turnover Renal Stone Risk Serum and urine renal stone parameters Abdominal ultrasound for renal stones Serum and urine markers of bone resorption All measurements will be obtained pre and post flight with the exception of urine collections which will be performed pre, in and post-flight.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 8 Testing/Activity Overview Weekly alendronate pill (alendronate subjects only) 24-hr urine collections (at early, mid and late flight time points) for bone markers and renal stone parameters * Exercise and diet logging * Daily Vitamin D supplementation * QCT (hip) (x 2) DXA (whole body, regional scans) (x 5) * pQCT (lower leg) (x 5) Blood draws to measure bone markers / renal stone parameters (x 4) * 24-hr urine collections for bone markers, renal stone parameters (x 4) * Ultrasound imaging for renal calcification (x 1) QCT (hip) (x 1) DXA (whole body + regional) (x 1) * pQCT (lower leg) (x 1) Blood draws to verify pre- dosing health status, measure bone markers/renal stone parameters, and perform post- infusion (zol. acid) monitoring (x 3 to 4) * 24-hr urine collections for bone markers and renal stone parameters (x 2) * Ultrasound imaging for renal Calcification (x 1) * Daily calcium and Vitamin D supplementation Pre FlightIn FlightPost Flight * Full or partial data/activity share with existing requirements

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 9 Equipment Overview (In Flight) Urine collection hardware: Described later in Urine Collection Training Alendronate kit (alendronate subjects only): Described later in Alendronate Ingestion Training

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 10 Possible Risks and Discomforts

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 11 Risks and Discomforts (cont’d)

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 12 Video/Photo Requirements Alendronate subjects will take a digital photo of the alendronate pill card(s) and comment card(s) during the final week of flight.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 13 Bisphosphonates : Urine Collection and Pill Ingestion Hardware Overview Curtis Kershner Rev. March 02, 2007

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 14 Class Objectives Identify and describe the contents and function of the urine collection kits Identify additional station hardware required to implement the experiment protocol Identify requirements for successful experiment implementation Draw a simulated urine sample, label, scan, and bag it for stowage

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 15 Urine Collection Kit (UCK): Urine Collection Device Biocide Wipes, Gauze, Quick disconnect Urine Sample Syringes Urine Collection Device (male condom catheter held at left) Urine Sample Syringes

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 16 Urine Collection Device (UCD) Designed with adapters for males or females at one end A blue sample port is at the other end Sample syringe tips are inserted into the blue port to remove samples Contains Lithium Chloride (LiCl) volume marker Urine voids must be mixed thoroughly with LiCl before sample removal Sample port Urine Collection Device: one UCD will be used for every void. Male adaptor (urine entry point)

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 17 Urine Sample Syringes Two Sample Syringes will be filled per void. (The tips are capped in this picture) Sample Syringe: tip at right (cap is removed) is inserted into UCD sample port. Plunger at left is extended to draw sample into syringe.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 18 Urine Containment Bag After Sample Syringes are filled from a urine collection device, the urine collection device should be returned to a sealed Bitran bag and disposed of in the Urine Containment Bag (below)

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 19 Session Breakdown Void by Void 24 Urine Collection One session be scheduled Early, Mid, and Late Mission for a total of three sessions. Begins with first urine void after waking on day 1. After each void, two Sample Syringes are filled and stowed in MELFI at -80˚C. Sample Syringes must be labeled with Crew ID and GMT. Sample Syringes must be scanned with Bar Code Reader or PDA using Experiment Ops field and proper Crew ID Each pair of Sample Syringes must be placed in sealed ziplock bags and wrapped with Kapton tape prior to MELFI insertion 24 hour collection ends with first morning void on day 2.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 20 Urine Collection Session Breakdown Void by Void 24 Urine Collection: in pictures Void into Urine Collection Device and knead bag to mix. Insert Sample Syringe into blue port of Urine Collection Device Draw sample until internal end of plunger is at the top of the blue velcro dot. Scan samples into Exp Ops, seal in Ziplock, Wrap with Kapton tape Place sample syringes in MELFI Reseal remaining urine in its Bitran bag and dispose in Urine Containment Bag

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 21 Alendronate Kit 8 Pill Cards (may vary based on crew participation) 4 Comment Cards Fine Point Sharpie

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 22 Alendronate Kit Alendronate Kit: Training kit with Pill Cards Pill Card : Training card with candy

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 23 In-flight Pill Ingestion Session Fast Overnight Unstow Alendronate Kit Unstow Pill Card Ingest (do not chew) pill with minimum of 8 oz. of water Do not eat or drink anything 30 minutes after pill ingestion except water If any anomalies (missed pills, etc) arise with ingestion, unstow comment card and document issue or concern If any symptoms (Upper GI symptoms) arise with ingestion, this information should be relayed as soon as practical to the Crew Surgeon via Private Medical Conference or other means.

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 24 Run Through Procedures

Urine Collection and Pill Ingestion E255/SMO 021 Bisphosphonates Johnson Space Center, Houston, Texas Curtis KershnerKaren Lawrence 25 Highlights Summary Urine Collection Mix LiCl with urine thoroughly Label syringes with Sharpie Scan syringes into Experiment Ops section of the barcode reader Don’t over fill the syringes Practice Voiding into the UCD at home, so you are comfortable as possible on orbit Alendronate Pill Ingestion Adhere to fasting constraints prior to Alendronate ingestion Take alendronate pill with at least 8 ounces of water Adhere to no food or drink except water constraint after pill ingestion During preflight dosing period and in flight, take all required supplements (Ca and Vit D preflight; Vit D in flight)