Re: SPRINTT project: who are we treating, people with frailty or those with sarcopenia?
Dear Editor,
In a recent randomized controlled trial (RCT) published in British Medical Journal (BMJ), Bernabei et al. [1] reported that a multicomponent intervention can reduce mobility disability in older adults with physical frailty and sarcopenia (PFS) and Short Physical Performance Battery (SPPB) score of 3-7. Some questionable issues emerged from this trial. The authors consider PF&S as a new nosological entity claiming the need to identify this condition to facilitate the development of clinical trials following the standards of drug research. In this scenario, we are concerned about the authors’ proposal to define a study population affected by a “concept” and not by a specific disease in RCTs. In our opinion, current diagnostic criteria for sarcopenia are based on robust scientific literature [2] thus not justifying the identification of a new syndrome for the enrollment of participants in clinical trials for muscle wasting interventions. Sarcopenia is often considered the main factor of progression toward frailty [3]. Moreover, although SPPB and 400 m walk test are recommended outcome measures of muscle function (i.e., physical performance not muscle strength) for the diagnosis of sarcopenia, the latest guidelines available on this topic [2], to which some of the authors of the paper also contributed, defined that these tools may not be necessary to diagnose sarcopenia, whereas measurements of muscle strength by a handheld dynamometer and appendicular lean mass (ALM) by dual-energy X-ray absorptiometry (DXA) are mandatory. The SPPB and the primary endpoint (400 m walk test) chosen by the authors can be used as an additional criterion for the diagnosis of severe sarcopenia in patients who have reported poor muscle strength and low ALM. Hence, choosing this “concept” for the definition of a study population would weaken the external validity of future RCTs.
Another issue emerged from the analysis of the intervention. Considering that resistance training is the most effective exercise type as well as the first-line therapy for sarcopenia [4], it is not clear how resistance to movement has been defined. In fact, authors declared that adjustable ankle weights were used to provide strengthening exercise for lower limbs, but they used Borg’s scale (more suitable for aerobic training) to measure the intensity of the exercise [1,5]. Strengthening typically requires external resistance to any physical activity which produces skeletal muscle contractions that are measured by the Repetition Maximum (maximal amount of weight that can be lifted for one complete repetition) [6-8]. Therefore, this methodological flaw in the description of the intervention, including no details about balance training, may represent a key limitation, also considering the significantly increased risk of falls in the multicomponent group (+62%) in patients with SPPB 3-7. Indeed, evidence suggests that fall risk is significantly reduced when an exercise program of at least 50 hours of challenging balance and progressive strength training, not including walking, is performed [9].
References
1. Bernabei R, Landi F, Calvani R, Cesari M, Del Signore S, Anker SD, Bejuit R, Bordes P, Cherubini A, Cruz-Jentoft AJ, Di Bari M, Friede T, Gorostiaga Ayestarán C, Goyeau H, Jónsson PV, Kashiwa M, Lattanzio F, Maggio M, Mariotti L, Miller RR, Rodriguez-Mañas L, Roller-Wirnsberger R, Rýznarová I, Scholpp J, Schols AMWJ, Sieber CC, Sinclair AJ, Skalska A, Strandberg T, Tchalla A, Topinková E, Tosato M, Vellas B, von Haehling S, Pahor M, Roubenoff R, Marzetti E; SPRINTT consortium. Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project). BMJ. 2022 May 11;377:e068788. doi: 10.1136/bmj-2021-068788.
2. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169. Erratum in: Age Ageing. 2019 Jul 1;48(4):601.
3. Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019 Jun 29;393(10191):2636-2646. doi: 10.1016/S0140-6736(19)31138-9. Epub 2019 Jun 3. Erratum in: Lancet. 2019 Jun 29;393(10191):2590.
4. Dent E, Morley JE, Cruz-Jentoft AJ, Arai H, Kritchevsky SB, Guralnik J, Bauer JM, Pahor M, Clark BC, Cesari M, Ruiz J, Sieber CC, Aubertin-Leheudre M, Waters DL, Visvanathan R, Landi F, Villareal DT, Fielding R, Won CW, Theou O, Martin FC, Dong B, Woo J, Flicker L, Ferrucci L, Merchant RA, Cao L, Cederholm T, Ribeiro SML, Rodríguez-Mañas L, Anker SD, Lundy J, Gutiérrez Robledo LM, Bautmans I, Aprahamian I, Schols JMGA, Izquierdo M, Vellas B. International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management. J Nutr Health Aging. 2018;22(10):1148-1161. doi: 10.1007/s12603-018-1139-9.
5. Landi F, Cesari M, Calvani R, Cherubini A, Di Bari M, Bejuit R, Mshid J, Andrieu S, Sinclair AJ, Sieber CC, Vellas B, Topinkova E, Strandberg T, Rodriguez-Manas L, Lattanzio F, Pahor M, Roubenoff R, Cruz-Jentoft AJ, Bernabei R, Marzetti E; SPRINTT Consortium. The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) randomized controlled trial: design and methods. Aging Clin Exp Res. 2017 Feb;29(1):89-100. doi: 10.1007/s40520-016-0715-2.
6. Hurst C, Robinson SM, Witham MD, Dodds RM, Granic A, Buckland C, De Biase S, Finnegan S, Rochester L, Skelton DA, Sayer AA. Resistance exercise as a treatment for sarcopenia: prescription and delivery. Age Ageing. 2022 Feb 2;51(2):afac003. doi: 10.1093/ageing/afac003.
7. Borde R, Hortobagyi T, Granacher U. Dose-Response Relationships of Resistance Training in Healthy Old Adults: A Systematic Review and Meta-Analysis. Sports medicine (Auckland, NZ). 2015;45(12):1693-720.
8. Manini TM, Clark BC, Tracy BL, Burke J, Ploutz-Snyder L. Resistance and functional training reduces knee extensor position fluctuations in functionally limited older adults. European journal of applied physiology. 2005;95(5-6):436-46.
9. Sherrington C, Whitney JC, Lord SR, Herbert RD, Cumming RG, Close JCT. Effective exercise for the prevention of falls: a systematic review and meta-analysis. J Am Geriatr Soc 2008; 56: 2234–43.
Competing interests:
No competing interests
20 May 2022
Giovanni Iolascon
Full Professor of Physical and Rehabilitation Medicine
Rapid Response:
Re: SPRINTT project: who are we treating, people with frailty or those with sarcopenia?
Dear Editor,
In a recent randomized controlled trial (RCT) published in British Medical Journal (BMJ), Bernabei et al. [1] reported that a multicomponent intervention can reduce mobility disability in older adults with physical frailty and sarcopenia (PFS) and Short Physical Performance Battery (SPPB) score of 3-7. Some questionable issues emerged from this trial. The authors consider PF&S as a new nosological entity claiming the need to identify this condition to facilitate the development of clinical trials following the standards of drug research. In this scenario, we are concerned about the authors’ proposal to define a study population affected by a “concept” and not by a specific disease in RCTs. In our opinion, current diagnostic criteria for sarcopenia are based on robust scientific literature [2] thus not justifying the identification of a new syndrome for the enrollment of participants in clinical trials for muscle wasting interventions. Sarcopenia is often considered the main factor of progression toward frailty [3]. Moreover, although SPPB and 400 m walk test are recommended outcome measures of muscle function (i.e., physical performance not muscle strength) for the diagnosis of sarcopenia, the latest guidelines available on this topic [2], to which some of the authors of the paper also contributed, defined that these tools may not be necessary to diagnose sarcopenia, whereas measurements of muscle strength by a handheld dynamometer and appendicular lean mass (ALM) by dual-energy X-ray absorptiometry (DXA) are mandatory. The SPPB and the primary endpoint (400 m walk test) chosen by the authors can be used as an additional criterion for the diagnosis of severe sarcopenia in patients who have reported poor muscle strength and low ALM. Hence, choosing this “concept” for the definition of a study population would weaken the external validity of future RCTs.
Another issue emerged from the analysis of the intervention. Considering that resistance training is the most effective exercise type as well as the first-line therapy for sarcopenia [4], it is not clear how resistance to movement has been defined. In fact, authors declared that adjustable ankle weights were used to provide strengthening exercise for lower limbs, but they used Borg’s scale (more suitable for aerobic training) to measure the intensity of the exercise [1,5]. Strengthening typically requires external resistance to any physical activity which produces skeletal muscle contractions that are measured by the Repetition Maximum (maximal amount of weight that can be lifted for one complete repetition) [6-8]. Therefore, this methodological flaw in the description of the intervention, including no details about balance training, may represent a key limitation, also considering the significantly increased risk of falls in the multicomponent group (+62%) in patients with SPPB 3-7. Indeed, evidence suggests that fall risk is significantly reduced when an exercise program of at least 50 hours of challenging balance and progressive strength training, not including walking, is performed [9].
References
1. Bernabei R, Landi F, Calvani R, Cesari M, Del Signore S, Anker SD, Bejuit R, Bordes P, Cherubini A, Cruz-Jentoft AJ, Di Bari M, Friede T, Gorostiaga Ayestarán C, Goyeau H, Jónsson PV, Kashiwa M, Lattanzio F, Maggio M, Mariotti L, Miller RR, Rodriguez-Mañas L, Roller-Wirnsberger R, Rýznarová I, Scholpp J, Schols AMWJ, Sieber CC, Sinclair AJ, Skalska A, Strandberg T, Tchalla A, Topinková E, Tosato M, Vellas B, von Haehling S, Pahor M, Roubenoff R, Marzetti E; SPRINTT consortium. Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project). BMJ. 2022 May 11;377:e068788. doi: 10.1136/bmj-2021-068788.
2. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169. Erratum in: Age Ageing. 2019 Jul 1;48(4):601.
3. Cruz-Jentoft AJ, Sayer AA. Sarcopenia. Lancet. 2019 Jun 29;393(10191):2636-2646. doi: 10.1016/S0140-6736(19)31138-9. Epub 2019 Jun 3. Erratum in: Lancet. 2019 Jun 29;393(10191):2590.
4. Dent E, Morley JE, Cruz-Jentoft AJ, Arai H, Kritchevsky SB, Guralnik J, Bauer JM, Pahor M, Clark BC, Cesari M, Ruiz J, Sieber CC, Aubertin-Leheudre M, Waters DL, Visvanathan R, Landi F, Villareal DT, Fielding R, Won CW, Theou O, Martin FC, Dong B, Woo J, Flicker L, Ferrucci L, Merchant RA, Cao L, Cederholm T, Ribeiro SML, Rodríguez-Mañas L, Anker SD, Lundy J, Gutiérrez Robledo LM, Bautmans I, Aprahamian I, Schols JMGA, Izquierdo M, Vellas B. International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management. J Nutr Health Aging. 2018;22(10):1148-1161. doi: 10.1007/s12603-018-1139-9.
5. Landi F, Cesari M, Calvani R, Cherubini A, Di Bari M, Bejuit R, Mshid J, Andrieu S, Sinclair AJ, Sieber CC, Vellas B, Topinkova E, Strandberg T, Rodriguez-Manas L, Lattanzio F, Pahor M, Roubenoff R, Cruz-Jentoft AJ, Bernabei R, Marzetti E; SPRINTT Consortium. The "Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies" (SPRINTT) randomized controlled trial: design and methods. Aging Clin Exp Res. 2017 Feb;29(1):89-100. doi: 10.1007/s40520-016-0715-2.
6. Hurst C, Robinson SM, Witham MD, Dodds RM, Granic A, Buckland C, De Biase S, Finnegan S, Rochester L, Skelton DA, Sayer AA. Resistance exercise as a treatment for sarcopenia: prescription and delivery. Age Ageing. 2022 Feb 2;51(2):afac003. doi: 10.1093/ageing/afac003.
7. Borde R, Hortobagyi T, Granacher U. Dose-Response Relationships of Resistance Training in Healthy Old Adults: A Systematic Review and Meta-Analysis. Sports medicine (Auckland, NZ). 2015;45(12):1693-720.
8. Manini TM, Clark BC, Tracy BL, Burke J, Ploutz-Snyder L. Resistance and functional training reduces knee extensor position fluctuations in functionally limited older adults. European journal of applied physiology. 2005;95(5-6):436-46.
9. Sherrington C, Whitney JC, Lord SR, Herbert RD, Cumming RG, Close JCT. Effective exercise for the prevention of falls: a systematic review and meta-analysis. J Am Geriatr Soc 2008; 56: 2234–43.
Competing interests: No competing interests