KNEE CARTILAGE QUALITY AND TYPE II COLLAGEN METABOLISM IN RESPONSE TO 21-DAYS BED REST IMMOBILIZATION

INTRODUCTION
The detrimental effects of immobilization and microgravity on articular cartilage are not well understood. This
aimed to investigate the effects of 21 days of head-down-tilt bed rest (HDT) (with and without exercise and
nutrition interventions) on type II collagen metabolism and on knee cartilage quality.
METHODS
Participants were exposed to 21 days of HDT + interventions (control (CON); resistive vibration exercise
(RVE); whey protein and bicarbonate supplementation + RVE (NeX) [1]. Twelve healthy male subjects (age
34.2±8.3 years; BMI 22.4±1.7 kg/m²) participated in the cross-over designed study. Blood and urine samples
were collected before, during and after HDT. Serum CPII, C2C, C1,2C and urinary CTX-II and Coll2-1NO2
concentrations were measured by enzyme-linked immunosorbent assays. T2 sequences of the knee joint were
obtained at BDC-7, HDT21 and R+6 and segmented by a blinded, independent service provider
(Chondrometrics GmbH, Freilassing, Germany) and T2Me computed for the deep (D) and superficial (S) zones
of the following regions: central medial and lateral femur (cMF, cLF), medial and lateral tibia (MT, LT).
Changes in response to HDT and countermeasures for type II collagen biomarkers and T2Me were evaluated
using linear mixed-effects models.
RESULTS
21 days of HDT resulted in increased serum CPII (p<0.001), C2C (p<0.001) and C1,2C (p= 0.001)
concentrations (highest increases: sCPII (+24.2% - HDT5), sC2C (+24.4% - HDT7), sC1,2C (+13.5% - HDT2)
and affected the ratio CPII:C2C ratio (p<0.001). Serum C2C remained elevated at R+1 (p=0.002) and R+6
(p<0.001) compared to baseline. NeX resulted in lower serum CPII (p<0.001) and C1,2C concentrations (p=
0.003) compared to CON. uCTX-II in 2nd void and 24 hours urine increased during HDT (p<0.001, highest
increase on HDT21: 2ndvoid +82.8% (p<0.001); 24hours urine +77.8% (p<0.001). NeX resulted in lower
uCTX-II concentrations in 24 hours urine (p=0.012) compared to CON. T2Me in the central medial femur
superficial layer (cMFST2Me) changed over time (p=0.038), with a decrease of 2.1% ((95% confidence
interval of the difference (95%CI) CI: [-2.4%; -2.0%]) at R+6 compared to BDC-7 (p=0.014, Table 1). The
cumulative effect of all campaigns (3*3 weeks of HDT-BR; R+6 of C3 vs. BDC-7 of C1) within 12 months
was a decrease in T2Me in the medial tibia superficial layer (MTST2Me, -2.6% (95%CI: [-3.1%; -2.3%],
p=0.037) and an increase in T2Me in the central lateral femur deep layer (cLFDT2Me, +3.1% 95%CI: [2.8%;
3.5%], p=0.039; Figure 1). Neither countermeasures affected T2Me in any of the cartilage regions.
CONCLUSIONS
21-days of HDT resulted in pronounced type II collagen degradation (with minimal countermeasure effect) that
did not recover within 6 days of re-ambulation. T2 imaging suggests that cartilage quality is affected by 21
days of HDT. The accumulative effect of three 21-day HDTs within 12 months altered the T2 relaxation times
in the medial tibia superficial layer and the central lateral femur deep layer. The countermeasures applied did
not appear to affect T2 relaxation times. Our data confirm our previous findings for cartilage metabolites [2],
[3], [4] and suggest that even shorter periods of immobilization result in systematic changes in articular
cartilage that are detectable by serum biomarker concentrations of type II collagen metabolism and MRI.
REFERENCES [1] Liphardt A.M. et al. (2019) Transl Sports Medicine 3, 93-10, [2] Liphardt AM, et al. (2018) J Orthop Res.
May;36(5):1465-1471. [3] Liphardt et al. (2020) J Orthop Res. Nov;38(11):2373-2382. [4] Liphardt et al. (2009) Osteoarthritis
Cartilage. Dec;17 (12):1598-603.