Tag Archive | growth factor

Sprifermin: Another Shot at Joint Preservation

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

To date, we have found only one documented disease-modifying intervention that slows the progression of knee osteoarthritis (OA)—weight loss.1 There are few positive findings about drugs or other therapeutic interventions that might prolong the life of the human joint. However, sprifermin, a recombinant human fibroblast growth factor that can be genetically engineered from bacteria, has been tested in a randomized proof-of-concept trial as an intra-articular injection in humans,2 with modestly promising results.

In a very recent study on the effect of sprifermin and several other potentially disease-modifying compounds on bovine chondrocytes, researchers used 3D cultures to assess chondrocyte proliferation and/or extracellular matrix production.3 All of the growth factors evaluated, including sprifermin, resulted in elevated markers of anabolic chondrocyte activity. For the most part, cyclic doses were more effective than continuous doses over 4 weeks. Of importance, only sprifermin decreased type I collagen expression and had no hypertrophic effects. The authors conclude in the abstract that “these results confirm that sprifermin is a promising disease-modifying OA drug.”

In a 5-year randomized human dose-finding trial,4 patients with symptomatic knee OA were divided into 5 groups, as follows:

  1. 100 μg of sprifermin administered every 6 months (n = 110)
  2. 100 μg of sprifermin administered every 12 months (n = 110)
  3. 30 μg of sprifermin administered every 6 months (n = 111)
  4. 30 μg of sprifermin administered every 12 months (n = 110)
  5. Placebo injections administered every 6 months (n = 108)

The greatest changes in the primary endpoint—increased total femorotibial joint cartilage thickness from baseline to 2 years—was 0.05 mm (95% CI, 0.03 to 0.07 mm) in the group that received 100 μg of sprifermin every 6 months and 0.04 mm (95% CI, 0.02 to 0.06 mm) in the group that received 100 μg of sprifermin every 12 months. However, compared with the placebo group, those receiving sprifermin had no statistically different change in WOMAC scores. On average, 40% of all the patients in the study experienced arthralgia associated with the injections.

More certainty about the efficacy, safety, and durability of sprifermin may come when data from the remaining 3 years of this study are analyzed (see ClinicalTrials.gov identifier NCT01919164).

References

  1. Gersing AS, Solka M, Joseph GB, Schwaiger BJ, Heilmeier U, Feuerriegel G, Nevitt MC, McCulloch CE, Link TM. Progression of cartilage degeneration and clinical symptoms in obese and overweight individuals is dependent on the amount of weight loss: 48-month data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016 Jul;24(7):1126-34. doi: 10.1016/j.joca.2016.01.984. PMID: 26828356 PMCID: PMC4907808.
  2. Lohmander LS, Hellot S, Dreher D, et al. 2014. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 66(7):1820–31.
  3. Müller S, Lindemann S, Gigout A. Effects of sprifermin, IGF1, IGF2, BMP7 or CNP on bovine chondrocytes in monolayer and 3D culture. J Orthop Res. 2019 Oct 14. doi: 10.1002/jor.24491. [Epub ahead of print] PMID: 31608492.
  4. Hochberg MC, Guermazi A, Guehring H, Aydemir A, Wax S, Fleuranceau-Morel P, Bihlet AR, Byrjalsen I, Andersen JR, Eckstein F. Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With OsteoarthritisThe FORWARD Randomized Clinical Trial. JAMA. 2019;322(14):1360-1370. doi:10.1001/jama.2019.14735

JBJS 100: THA Registries, Bone-Repair Growth Factors

JBJS 100Under one name or another, The Journal of Bone & Joint Surgery has published quality orthopaedic content spanning three centuries. In 1919, our publication was called the Journal of Orthopaedic Surgery, and the first volume of that journal was Volume 1 of what we know today as JBJS.

Thus, the 24 issues we turn out in 2018 will constitute our 100th volume. To help celebrate this milestone, throughout the year we will be spotlighting 100 of the most influential JBJS articles on OrthoBuzz, making the original content openly accessible for a limited time.

Unlike the scientific rigor of Journal content, the selection of this list was not entirely scientific. About half we picked from “JBJS Classics,” which were chosen previously by current and past JBJS Editors-in-Chief and Deputy Editors. We also selected JBJS articles that have been cited more than 1,000 times in other publications, according to Google Scholar search results. Finally, we considered “activity” on the Web of Science and The Journal’s websites.

We hope you enjoy and benefit from reading these groundbreaking articles from JBJS, as we mark our 100th volume. Here are two more, both from 2002:

The Swedish Total Hip Replacement Register
H Malchau, P Herberts, T Eisler, G Garellick, P Soderman: JBJS, 2002 November; 84 (Suppl 2): S2
In this 19-page analysis of data from the Swedish Total Hip Replacement Register, which was initiated in 1979, Malchau et al. pinpoint the striking clinical and socioeconomic effects of the Register’s first 20 years. The information captured by joint registries, especially in regions that provide universal health care coverage and thus maintain robust databases, has helped orthopaedic surgeons refine indications, surgical techniques, and implant choices.

The Role of Growth Factors in the Repair of Bone: Biology and Clinical Applications
J R Lieberman, A Daluiski, T A Einhorn: JBJS, 2002 June; 84 (6): 1032
Countless studies related to tissue engineering and the musculoskeletal system have been published in the 16 years since this Current Concepts Review  appeared in JBJS. Yet this article remains an essential primer for understanding how growth factors affect cells and tissues—and the possible applications for using growth factors to accelerate fracture healing, treat nonunions, and enhance spinal fusion.

What’s New in Foot and Ankle Surgery

Every month, JBJS publishes a Specialty Update—a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all OrthoBuzz Specialty Update summaries.

This month, OrthoBuzz asked Sheldon Lin, MD and Michael Yeranosian, MD, co-authors of the May 18, 2016 Specialty Update on foot and ankle surgery, to select the five most clinically compelling findings from among the more than 50 studies they cited.

Ankle Fractures and Syndesmotic Injuries

–A randomized study compared syndesmotic fixation versus no fixation in patients with supination-external rotation (SER) IV-type ankle fractures and positive intraoperative stress tests (persistent widening of the medial clear space). At four years of follow-up researchers found no clinical or radiological differences between the two groups.1

–A randomized single-blinded trial to help determine optimal methods for soft-tissue management after ankle trauma compared standard treatment using ice and elevation with the use of multilayer compression bandages. Researchers found that multilayer compression therapy resulted in faster resolution of edema than cryotherapy.

Total Ankle Arthroplasty

–A prospective cohort study found that patients undergoing total ankle arthroplasty (TAA) had higher preoperative expectation scores than did those undergoing ankle arthrodesis. TAA patients were also more likely than arthrodesis patients to report improved postoperative satisfaction scores. Postoperative expectation and satisfaction scores in both groups were closely linked to postoperative Ankle Osteoarthritis Scale (AOS) scores. The study emphasizes the importance of preoperative patient education.2

Orthobiologics

–A randomized controlled trial looking at union rates in ankle and hindfoot arthrodesis compared the use of recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) plus an injectable osteoconductive beta-tricalcium phosphate (β-TCP) collagen matrix to standard autograft.  Complete fusion of all involved joints at 24 weeks occurred in 84% of those treated with the growth factor-matrix combination and in 65% of those treated with autograft (p <0.001).3

Patient-Reported Outcomes Assessment

–The 10-center Orthopaedic Foot & Ankle Outcomes Research (OFAR) Network conducted a three-month trial of collecting preoperative and six-month postoperative patient outcome information using the Patient Reported Outcomes Measurement Information System (PROMIS). Of the 328 patients enrolled, 76% completed the preoperative instruments and 43% completed the six-month postoperative instruments. Despite substantial loss to follow-up, the OFAR Network process enabled easy data aggregation and analysis, suggesting its utility in facilitating multicenter trials.4

References

  1. Kortekangas THJ, Pakarinen HJ, Savola O, Niinimäki J, Lepojärvi S, Ohtonen P, Flinkkilä T, Ristiniemi J. Syndesmotic fixation in supination-external rotation ankle fractures: a prospective randomized study. Foot Ankle Int. 2014 Oct;35(10):988-95. Epub 2014 Jun 24.
  1. Younger ASE, Wing KJ, Glazebrook M, Daniels TR, Dryden PJ, Lalonde KA, Wong H, Qian H, Penner M. Patient expectation and satisfaction as measures of operative outcome in end-stage ankle arthritis: a prospective cohort study of total ankle replacement versus ankle fusion. Foot Ankle Int. 2015 Feb;36(2):123-34.
  1. Daniels TR, Younger ASE, Penner MJ, Wing KJ, Le ILD, Russell IS, Lalonde KA, Evangelista PT, Quiton JD, Glazebrook M, DiGiovanni CW. Prospective randomized controlled trial of hindfoot and ankle fusions treated with rhPDGF-BB in combination with a β-TCP-collagen matrix. Foot Ankle Int. 2015 Jul;36(7):739-48.Epub 2015 Apr 6.
  1. Hunt KJ, Alexander I, Baumhauer J, Brodsky J, Chiodo C, Daniels T, Davis WH, Deland J, Ellis S, Hung M, Ishikawa SN, Latt LD, Phisitkul P, SooHoo NF, Yang A, Saltzman CL; OFAR (Orthopaedic Foot and Ankle Outcomes Research Network). The Orthopaedic Foot and Ankle Outcomes Research (OFAR) network: feasibility of a multicenter network for patient outcomes assessment in foot and ankle. Foot Ankle Int. 2014Sep;35(9):847-54.