Harold M. Frost T J Musculoskel Neuron Interact 2001; 2(2):117-119 William F. Neuman Awardee 2001

Tribute to Harold M. Frost, honorary president of ISMNI, who received the William F. Neuman Award from the American Society of Bone and Mineral Research October 2001

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass.Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass

Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10−6. The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks

Immobilization and retraining of cruciate ligaments in the rat

Fifty male rats, aged 40 days, were assigned to one of five groups to examine the influence of immobilization and retraining on the strength and elastic stiffness of the anterior and posterior cruciate ligaments. Following the experimental treatments, the anterior ligament from the right leg and the posterior ligament from the left leg were tested in tension at a separation speed of 50 mm/min. After 4 weeks of cast immobilization, the separation force of the anterior ligament declined by one fourth and elastic stiffness of both ligaments declined by one fourth and one third, respectively. No changes occurred in the separation force of the posterior ligament. Following a 6-week retraining swimming program, the separation force and elastic stiffness values had returned to control levels. Additionally, there was a transition from avulsion type failures in the immobilized groups of animals to insertion site and intraligament failures in animals subjected to rehabilitative swimming exercise. This was indicative of a return in the strength of the osseous component of the bone-ligament-bone complex following immobilization

The influence of hand guards on forces and muscle activity during giant swings on the high bar

To investigate the influence of hand guards on the loads experienced by gymnasts during giant swings on the high bar, forces applied to the bar by each hand and muscle activity of the extrinsic finger flexor and wrist extensor muscle groups were measured in 10 male gymnasts as they completed a minimum of three backward giant swings on the high bar. Measurements were made under four conditions of performance: bare hands, with webbing loops, with doweled hand guards (DHG), and a wind-up swing using DHG. Peak reaction forces at the hands were of the order of 2.2 times body weight (BW) on each hand, and were significantly (P < 0.05) lower when swinging bare-handed, compared with the other three conditions. By contrast, the integrated electromyograms showed that both wrist flexor and extensor muscle activity was unchanged across conditions. These results indicate that the use of hand guards allows greater tensile forces to act across the wrist without a measurable increase in forearm muscle activity. Thus, it is possible that there is extra stress on the ligaments of the wrist or at the epiphyseal plates. In adolescent and preadolescent gymnasts, the additional tension on the distal epiphyses of the radius and ulna may have implications for bone growth