Archives of Gerontology and Geriatrics 60 (2015) 349–353
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger
Secondary hyperparathyroidism and its relationship with sarcopenia in elderly women Patrı´cia de Souza Genaro a, Marcelo de Medeiros Pinheiro b, Vera Lu´cia Szejnfeld b, Lı´gia Arau´jo Martini a,* a b
Nutrition Department, School of Public Health, University of Sa˜o Paulo, Av Dr Arnaldo, 715, Sa˜o Paulo 01246904, SP, Brazil Rheumatology Division, Sa˜o Paulo Federal University, Sa˜o Paulo, SP, Brazil
A R T I C L E I N F O
A B S T R A C T
Article history: Received 16 September 2013 Received in revised form 23 December 2014 Accepted 6 January 2015 Available online 13 January 2015
Low dietary intake of calcium and poor vitamin D status during aging can result in mild secondary hyperparathyroidism, which may be associated with low muscle mass and reduced strength in the elderly. The aim of this study was to investigate whether low vitamin D, high parathormone (PTH), or both, are associated with sarcopenia. A total of 105 women, 35 with sarcopenia and 70 without sarcopenia, were enrolled in the present study. Body composition measurements were performed by DXA and sarcopenia was defined as skeletal muscle mass index < 5.45 kg/m2 and grip strength lower than 20 kg. Three-day dietary records were taken and adjustments for energy intake made. The estimated average requirement (EAR) method was adopted as a cut-off point for estimating the prevalence of inadequate intake. Serum total calcium, phosphorus, creatinine, intact PTH, and 25(OH)D were measured. Only 1% of the patients met the daily adequate intake for vitamin D and 11% met the daily adequate intake for calcium. Notably, the prevalence of sarcopenia was higher in hyperparathyroidism (25(OH)D < 20 ng/mL and PTH > 65 pg/dL) than in the absence of hyperparathyroidism (41.2 vs 16.2%, respectively; p = 0.046). The odds ratio for sarcopenia in hyperparathyroidism cases was 6.81 (95%CI 1.29–35.9) compared with participants who had low PTH and a high 25(OH)D concentration. The present study showed that vitamin D insufficiency associated with secondary hyperparathyroidism increased the risk of sarcopenia, suggesting that the suppression of hyperparathyroidism by ensuring adequate calcium and vitamin D intake should be considered in interventional studies to confirm potential benefits. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Vitamin D deficiency Parathormone Muscle mass Elderly Body composition
1. Introduction Ageing is associated with a progressive decline in muscle mass and strength, a condition known as sarcopenia (Cruz-Jentoft et al., 2010a). This condition increases the risk for functional limitations and mortality (Heitmann, Erikson, Ellsinger, Mikkelsen, & Larsson, 2000; Visser et al., 2002). Identifying the determinants of decline in muscle mass and strength is important and age-related changes in concentrations of both 25-hydroxyvitamin D 25(OH)D and parathyroid hormone (PTH) may play a role in sarcopenia. In the past decade, the literature has shown that vitamin D deficiency is common in the elderly (Holick, 2007; Mithal et al., 2009) and, despite a lack of consensus on the identification of
* Corresponding author. Tel.: +55 11 3061 7859; fax: +55 11 3061 7771. E-mail address: [email protected] (L.A. Martini). http://dx.doi.org/10.1016/j.archger.2015.01.005 0167-4943/ß 2015 Elsevier Ireland Ltd. All rights reserved.
vitamin D receptor (VDR) in muscle cells (Bischoff et al., 2001; Wang & DeLuca, 2011), vitamin D deficiency is associated with decline in muscle strength, often leading to marked disability and falls (Pfeifer et al., 2001a). Furthermore, vitamin D supplementation studies in older adults with vitamin D deficiency have shown improvements in physical function, increases in strength and decreases in falls (Bischoff-Ferrari et al., 2004a). Additionally, PTH levels increase with age (Need, Horowitz, Morris, & Nordin, 2000). Higher PTH levels in nursing home patients have been associated with falls, independently of 25(OH)D (Stein et al., 1999). Low vitamin D status, reduced renal function, and low dietary intake of calcium can result in mild secondary hyperparathyroidism, which may be associated with low muscle mass and reduced muscle strength in elderly populations. The aim of the present study was to investigate whether low vitamin D, high PTH, or both, are associated with sarcopenia.
350
P.S. Genaro et al. / Archives of Gerontology and Geriatrics 60 (2015) 349–353
2. Methods
2.5. Laboratory measurements
2.1. Subjects Women aged over 65 years were screened from February 2007 to December 2008. Recruitment was conducted by telephone in 315 patients who had undergone bone densitometry at the Rheumatology Division of Sa˜o Paulo Hospital, Federal University of Sao Paulo. Women older than 65 years were invited to participate. History of chronic renal failure, alcohol abuse, stroke, chronic pulmonary disease, myocardial infarction, and diagnosis of cancer, Parkinson’s disease, arthritis, or use of protein supplements were exclusion criteria. Furthermore, patients not living in the metropolitan area of Sa˜o Paulo or refusing to participate were also excluded (n = 10). The study was approved by the local research ethics committee and all participants gave their informed consent prior to inclusion in the study. A total of 105 women, 35 with sarcopenia and 70 without sarcopenia matched for age and weight, were enrolled in the present study.
An overnight fasting blood sample was obtained from each elderly woman. After blood coagulation and centrifugation at 2000 rpm for 10 min at room temperature, the serum samples were harvested and frozen at 80 8C pending analyses for serum total calcium, phosphorus, creatinine, intact PTH, and 25(OH)D. All exams were measured by automated standard laboratory methods. Creatinine, calcium and phosphorus were measured by colorimetric assay. Serum intact PTH concentrations were measured using electrochemiluminescence immunoassay (Cobas E411 Roche); the normal range in adults is 6–65 pg/mL, with an interassay coefficient of variation of 7.0–9.2%. Serum 25-hydroxyvitamin D concentration was measured using high performance liquid chromatography (HPLC; Immundiagnostik AG, Germany), with an interassay coefficient of variation of 7.5–9.6%. Vitamin D deficiency was defined as 25(OH)D concentration 65 pg/mL.
2.2. Anthropometric and body composition measurements
2.6. Other covariates
Weight, height and body mass index (BMI) were determined using standard techniques. BMI was calculated by dividing weight (kg) by the square of height (m2). Body composition was assessed using dual-energy X-ray absorptiometry (DXA–GE-Lunar DPX-MD plus, Madison, WI, USA, version 8.5 software). Sarcopenia was defined based on appendicular skeletal muscle mass (ASMM) measurements (Baumgartner et al., 1998). ASMM corresponds to the sum of the 2 upper and lower limb lean masses in kilograms. ASMM was normalized for height (ASMM/height2). Women whose relative appendicular skeletal muscle mass was >2 standarddeviations below the mean of a reference population from the Rosetta Study, which included 284 healthy Americans aged 18– 40 y (Gallagher et al., 1997), were classified as having sarcopenia. The cut-off corresponded to 5.45 kg/m2 in women.
A questionnaire was used to collect information on personal habits and medical history. Participants answered questions on: smoking habits including (current, past and never); calcium and vitamin D supplement use (yes/no); and 3 months’ regular physical activity, considered positive when participants reported physical exercise or sport of moderate intensity for at least 30 min a day on five or more days a week, or exercise or sport of vigorous intensity for at least 20 min a day in at least three days a week and/or performance of household chores (World Health Organization, 2004; Pate et al., 1995). A fall was defined as inadvertently coming to rest on the ground or other lower level without loss of consciousness and other than as a consequence of sudden onset of paralysis, epileptic seizure, while two or more falls in the previous year was defined as recurrent falls. Congestive heart disease, hypertension, dyslipidemia, and diabetes were considered chronic diseases.
2.3. Grip strength Grip strength was used as an indicator of muscle strength and is known to be positively correlated with both lower-extremity and upper-body strength in older persons, with reported correlation coefficients between 0.47 and 0.63 (Kallman, Plato, & Tobin, 1990). Grip strength was measured using a grip strength dynamometer (Jamar1 Hydraulic Hand Dynamometer). Three measurements were taken on the dominant side of the body with a one-minute interval between readings. The average of the three values was registered (Harkonen, Harju, & Alaranta, 1990). Sarcopenia was defined when strength was lower than 20 kg (Cruz-Jentoft et al., 2010b). 2.4. Dietary intake Three-day dietary records were used to estimate mean protein, calcium, phosphorus and vitamin D intakes. Dietary intakes were analyzed using the Nutrition Data System for Research (2007), developed by the Nutrition Coordinating Center (NCC), University of Minnesota, Minneapolis, MN. For all analyses, adjustments for dietary energy were made based on the residual nutrient method proposed by Willett and Stampfer (1998). The estimated average requirement (EAR) method, where the probability of inadequacy is calculated for an individual’s usual nutrient intake using the EAR and the standard deviation from the requirement, was adopted as the cut-off point for estimating the prevalence of inadequate intake in the population studied (Institute of Medicine, 2000).
2.7. Statistical analysis The descriptive data are expressed as mean (standard deviation). All variables had normal distribution according to the Kolmogorov–Smirnov test. The Student’s t-test was used to determine statistical differences among dietary, biochemical and body composition variables between women with and without sarcopenia. Additionally, Student’s t-test was also used to determine statistical differences of body composition in presence of hyperparathyroidism. The Chi-squared test was used to test association between presence of sarcopenia and prevalence of vitamin D deficiency (25(OH)D 65 pg/dL), and secondary hyperparathyroidism in women with and without sarcopenia. Logistic regression was performed to evaluate the odds ratio for secondary hyperparathyroidism, low vitamin D and high PTH in low grip strength and presence of sarcopenia adjusted for smoking, chronic diseases, season of data collection, physical activity level, protein intake and calcium supplementation. Statistical significance was assumed when p < 0.05. The software used was the Statistical Package for the Social Sciences version 11.0 for Windows (SPSS Inc., Chicago, IL, USA). 3. Results General characteristics variables are given in Table 1. There were no significant differences between groups with regard to the
P.S. Genaro et al. / Archives of Gerontology and Geriatrics 60 (2015) 349–353
351
Table 1 Characteristics of elderly women with and without sarcopenia. Characteristic
Total (n = 105)
No sarcopenia (n = 70)
Sarcopenia (n = 35)
Age (years) Weight (kg) Height (cm) BMI (kg/m2)
70.6 54.5 149.8 24.3
(5.2) (7.6) (6.0) (3.2)
70.6 55.0 149.1 24.7
(4.9) (7.2) (5.6) (2.8)
70.6 53.5 151.3 23.4
(5.7) (8.4) (6.4) (3.7)
1.000 0.354 0.071 0.062
Body composition Total muscle mass (kg) ASMM (kg) SMMI (kg/m2) Grip strength (kg) Fat mass (kg) Fat mass (%)
31.0 13.0 5.8 19.6 20.1 38.4
(3.4) (1.9) (0.7) (4.4) (5.9) (7.6)
32.1 13.7 6.1 20.4 19.9 40.6
(3.2) (1.7) (0.5) (4.3) (5.9) (7.8)
28.9 11.6 5.0 17.8 20.4 37.2
(2.7) (1.6) (0.3) (3.0) (6.1) (7.4)
20 ng/mL + PTH < 65 pg/dL (n = 41) 25(OH)D < 20 ng/mL + PTH > 65 pg/dL (n = 13)
Grip strength
Contents lists available at ScienceDirect
Archives of Gerontology and Geriatrics journal homepage: www.elsevier.com/locate/archger
Secondary hyperparathyroidism and its relationship with sarcopenia in elderly women Patrı´cia de Souza Genaro a, Marcelo de Medeiros Pinheiro b, Vera Lu´cia Szejnfeld b, Lı´gia Arau´jo Martini a,* a b
Nutrition Department, School of Public Health, University of Sa˜o Paulo, Av Dr Arnaldo, 715, Sa˜o Paulo 01246904, SP, Brazil Rheumatology Division, Sa˜o Paulo Federal University, Sa˜o Paulo, SP, Brazil
A R T I C L E I N F O
A B S T R A C T
Article history: Received 16 September 2013 Received in revised form 23 December 2014 Accepted 6 January 2015 Available online 13 January 2015
Low dietary intake of calcium and poor vitamin D status during aging can result in mild secondary hyperparathyroidism, which may be associated with low muscle mass and reduced strength in the elderly. The aim of this study was to investigate whether low vitamin D, high parathormone (PTH), or both, are associated with sarcopenia. A total of 105 women, 35 with sarcopenia and 70 without sarcopenia, were enrolled in the present study. Body composition measurements were performed by DXA and sarcopenia was defined as skeletal muscle mass index < 5.45 kg/m2 and grip strength lower than 20 kg. Three-day dietary records were taken and adjustments for energy intake made. The estimated average requirement (EAR) method was adopted as a cut-off point for estimating the prevalence of inadequate intake. Serum total calcium, phosphorus, creatinine, intact PTH, and 25(OH)D were measured. Only 1% of the patients met the daily adequate intake for vitamin D and 11% met the daily adequate intake for calcium. Notably, the prevalence of sarcopenia was higher in hyperparathyroidism (25(OH)D < 20 ng/mL and PTH > 65 pg/dL) than in the absence of hyperparathyroidism (41.2 vs 16.2%, respectively; p = 0.046). The odds ratio for sarcopenia in hyperparathyroidism cases was 6.81 (95%CI 1.29–35.9) compared with participants who had low PTH and a high 25(OH)D concentration. The present study showed that vitamin D insufficiency associated with secondary hyperparathyroidism increased the risk of sarcopenia, suggesting that the suppression of hyperparathyroidism by ensuring adequate calcium and vitamin D intake should be considered in interventional studies to confirm potential benefits. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Vitamin D deficiency Parathormone Muscle mass Elderly Body composition
1. Introduction Ageing is associated with a progressive decline in muscle mass and strength, a condition known as sarcopenia (Cruz-Jentoft et al., 2010a). This condition increases the risk for functional limitations and mortality (Heitmann, Erikson, Ellsinger, Mikkelsen, & Larsson, 2000; Visser et al., 2002). Identifying the determinants of decline in muscle mass and strength is important and age-related changes in concentrations of both 25-hydroxyvitamin D 25(OH)D and parathyroid hormone (PTH) may play a role in sarcopenia. In the past decade, the literature has shown that vitamin D deficiency is common in the elderly (Holick, 2007; Mithal et al., 2009) and, despite a lack of consensus on the identification of
* Corresponding author. Tel.: +55 11 3061 7859; fax: +55 11 3061 7771. E-mail address: [email protected] (L.A. Martini). http://dx.doi.org/10.1016/j.archger.2015.01.005 0167-4943/ß 2015 Elsevier Ireland Ltd. All rights reserved.
vitamin D receptor (VDR) in muscle cells (Bischoff et al., 2001; Wang & DeLuca, 2011), vitamin D deficiency is associated with decline in muscle strength, often leading to marked disability and falls (Pfeifer et al., 2001a). Furthermore, vitamin D supplementation studies in older adults with vitamin D deficiency have shown improvements in physical function, increases in strength and decreases in falls (Bischoff-Ferrari et al., 2004a). Additionally, PTH levels increase with age (Need, Horowitz, Morris, & Nordin, 2000). Higher PTH levels in nursing home patients have been associated with falls, independently of 25(OH)D (Stein et al., 1999). Low vitamin D status, reduced renal function, and low dietary intake of calcium can result in mild secondary hyperparathyroidism, which may be associated with low muscle mass and reduced muscle strength in elderly populations. The aim of the present study was to investigate whether low vitamin D, high PTH, or both, are associated with sarcopenia.
350
P.S. Genaro et al. / Archives of Gerontology and Geriatrics 60 (2015) 349–353
2. Methods
2.5. Laboratory measurements
2.1. Subjects Women aged over 65 years were screened from February 2007 to December 2008. Recruitment was conducted by telephone in 315 patients who had undergone bone densitometry at the Rheumatology Division of Sa˜o Paulo Hospital, Federal University of Sao Paulo. Women older than 65 years were invited to participate. History of chronic renal failure, alcohol abuse, stroke, chronic pulmonary disease, myocardial infarction, and diagnosis of cancer, Parkinson’s disease, arthritis, or use of protein supplements were exclusion criteria. Furthermore, patients not living in the metropolitan area of Sa˜o Paulo or refusing to participate were also excluded (n = 10). The study was approved by the local research ethics committee and all participants gave their informed consent prior to inclusion in the study. A total of 105 women, 35 with sarcopenia and 70 without sarcopenia matched for age and weight, were enrolled in the present study.
An overnight fasting blood sample was obtained from each elderly woman. After blood coagulation and centrifugation at 2000 rpm for 10 min at room temperature, the serum samples were harvested and frozen at 80 8C pending analyses for serum total calcium, phosphorus, creatinine, intact PTH, and 25(OH)D. All exams were measured by automated standard laboratory methods. Creatinine, calcium and phosphorus were measured by colorimetric assay. Serum intact PTH concentrations were measured using electrochemiluminescence immunoassay (Cobas E411 Roche); the normal range in adults is 6–65 pg/mL, with an interassay coefficient of variation of 7.0–9.2%. Serum 25-hydroxyvitamin D concentration was measured using high performance liquid chromatography (HPLC; Immundiagnostik AG, Germany), with an interassay coefficient of variation of 7.5–9.6%. Vitamin D deficiency was defined as 25(OH)D concentration 65 pg/mL.
2.2. Anthropometric and body composition measurements
2.6. Other covariates
Weight, height and body mass index (BMI) were determined using standard techniques. BMI was calculated by dividing weight (kg) by the square of height (m2). Body composition was assessed using dual-energy X-ray absorptiometry (DXA–GE-Lunar DPX-MD plus, Madison, WI, USA, version 8.5 software). Sarcopenia was defined based on appendicular skeletal muscle mass (ASMM) measurements (Baumgartner et al., 1998). ASMM corresponds to the sum of the 2 upper and lower limb lean masses in kilograms. ASMM was normalized for height (ASMM/height2). Women whose relative appendicular skeletal muscle mass was >2 standarddeviations below the mean of a reference population from the Rosetta Study, which included 284 healthy Americans aged 18– 40 y (Gallagher et al., 1997), were classified as having sarcopenia. The cut-off corresponded to 5.45 kg/m2 in women.
A questionnaire was used to collect information on personal habits and medical history. Participants answered questions on: smoking habits including (current, past and never); calcium and vitamin D supplement use (yes/no); and 3 months’ regular physical activity, considered positive when participants reported physical exercise or sport of moderate intensity for at least 30 min a day on five or more days a week, or exercise or sport of vigorous intensity for at least 20 min a day in at least three days a week and/or performance of household chores (World Health Organization, 2004; Pate et al., 1995). A fall was defined as inadvertently coming to rest on the ground or other lower level without loss of consciousness and other than as a consequence of sudden onset of paralysis, epileptic seizure, while two or more falls in the previous year was defined as recurrent falls. Congestive heart disease, hypertension, dyslipidemia, and diabetes were considered chronic diseases.
2.3. Grip strength Grip strength was used as an indicator of muscle strength and is known to be positively correlated with both lower-extremity and upper-body strength in older persons, with reported correlation coefficients between 0.47 and 0.63 (Kallman, Plato, & Tobin, 1990). Grip strength was measured using a grip strength dynamometer (Jamar1 Hydraulic Hand Dynamometer). Three measurements were taken on the dominant side of the body with a one-minute interval between readings. The average of the three values was registered (Harkonen, Harju, & Alaranta, 1990). Sarcopenia was defined when strength was lower than 20 kg (Cruz-Jentoft et al., 2010b). 2.4. Dietary intake Three-day dietary records were used to estimate mean protein, calcium, phosphorus and vitamin D intakes. Dietary intakes were analyzed using the Nutrition Data System for Research (2007), developed by the Nutrition Coordinating Center (NCC), University of Minnesota, Minneapolis, MN. For all analyses, adjustments for dietary energy were made based on the residual nutrient method proposed by Willett and Stampfer (1998). The estimated average requirement (EAR) method, where the probability of inadequacy is calculated for an individual’s usual nutrient intake using the EAR and the standard deviation from the requirement, was adopted as the cut-off point for estimating the prevalence of inadequate intake in the population studied (Institute of Medicine, 2000).
2.7. Statistical analysis The descriptive data are expressed as mean (standard deviation). All variables had normal distribution according to the Kolmogorov–Smirnov test. The Student’s t-test was used to determine statistical differences among dietary, biochemical and body composition variables between women with and without sarcopenia. Additionally, Student’s t-test was also used to determine statistical differences of body composition in presence of hyperparathyroidism. The Chi-squared test was used to test association between presence of sarcopenia and prevalence of vitamin D deficiency (25(OH)D 65 pg/dL), and secondary hyperparathyroidism in women with and without sarcopenia. Logistic regression was performed to evaluate the odds ratio for secondary hyperparathyroidism, low vitamin D and high PTH in low grip strength and presence of sarcopenia adjusted for smoking, chronic diseases, season of data collection, physical activity level, protein intake and calcium supplementation. Statistical significance was assumed when p < 0.05. The software used was the Statistical Package for the Social Sciences version 11.0 for Windows (SPSS Inc., Chicago, IL, USA). 3. Results General characteristics variables are given in Table 1. There were no significant differences between groups with regard to the
P.S. Genaro et al. / Archives of Gerontology and Geriatrics 60 (2015) 349–353
351
Table 1 Characteristics of elderly women with and without sarcopenia. Characteristic
Total (n = 105)
No sarcopenia (n = 70)
Sarcopenia (n = 35)
Age (years) Weight (kg) Height (cm) BMI (kg/m2)
70.6 54.5 149.8 24.3
(5.2) (7.6) (6.0) (3.2)
70.6 55.0 149.1 24.7
(4.9) (7.2) (5.6) (2.8)
70.6 53.5 151.3 23.4
(5.7) (8.4) (6.4) (3.7)
1.000 0.354 0.071 0.062
Body composition Total muscle mass (kg) ASMM (kg) SMMI (kg/m2) Grip strength (kg) Fat mass (kg) Fat mass (%)
31.0 13.0 5.8 19.6 20.1 38.4
(3.4) (1.9) (0.7) (4.4) (5.9) (7.6)
32.1 13.7 6.1 20.4 19.9 40.6
(3.2) (1.7) (0.5) (4.3) (5.9) (7.8)
28.9 11.6 5.0 17.8 20.4 37.2
(2.7) (1.6) (0.3) (3.0) (6.1) (7.4)
20 ng/mL + PTH < 65 pg/dL (n = 41) 25(OH)D < 20 ng/mL + PTH > 65 pg/dL (n = 13)
Grip strength
