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A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease
ARTICLE IN PRESS
Parkinsonism and Related Disorders 13 (2007) 355–358 www.elsevier.com/locate/parkreldis
A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson’s disease Marı´ a C. Ferna´ndeza, Muriel S. Parisia,b,, Sergio P. Dı´ azc, Silvina R. Mastagliaa,b, Juan M. Deferraria, Mariana Seijoa, Alicia Bagura, Federico Michelic, Beatriz Oliveria,b a
Department of Internal Medicine, Seccio´n Osteopatı´as Me´dicas, Hospital de Clı´nicas, Universidad de Buenos Aires, Co´rdoba 2351, 8 piso, (1120) Buenos Aires, Argentina b Researcher of the Consejo Nacional de Investigaciones Cientı´ficas y Tecnolo´gicas (CONICET), Argentina c Programa de Parkinson y Movimientos Anormales del Instituto de Neurociencias Aplicadas, Hospital de Clı´nicas, Universidad de Buenos Aires, Argentina Received 12 August 2006; received in revised form 30 November 2006; accepted 6 December 2006
Abstract The impact of body composition on bone and mineral metabolism in Parkinson’s disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (po0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels. r 2007 Elsevier Ltd. All rights reserved. Keywords: Parkinson’s disease; Vitamin D; Body composition; Bone mineral density
1. Introduction Patients with Parkinson’s disease (PD) are known to be at higher risk of fractures than healthy subjects [1–3]. Cumulative evidence indicates that this is related to several contributing factors, including increased rate of falls, reduced bone mineral density (BMD), reduced body mass index (BMI), and vitamin D deficiency [2,4–7]. Falls in PD are caused by many independent, albeit often coexistent, mechanisms such as postural instability, difficulty with transfer, gait disturbances and orthostatic syncope [8]. Consequently, fear of renewed falls may lead to a self-imposed restriction of daily activities causing immobility, which in turn is associated with osteoporosis and reduced fitness [9]. Corresponding author. Department of Internal Medicine, Seccio´n Osteopatı´ as Me´dicas, Hospital de Clı´ nicas, Universidad de Buenos Aires, Co´rdoba 2351, 8 piso (1120) Buenos Aires-Argentina. Tel.: 54 11 59508972; fax: 54 11 59508973. E-mail address: [email protected] (M.S. Parisi).
1353-8020/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2006.12.010
There are reports indicating that PD patients are at greater nutritional risk [10–12], and a recent study by Cheshire and Zbigniew [13] reported that reduced BMI is observed early in the course of the disease. Both the symptoms of the disease and medication side effects can limit food intake. Motor impairment secondary to PD itself can also affect body composition. Petroni et al. [14] described the presence of sarcopenic obesity, defined as an excess of fat tissue and a decrease in lean body mass, in advanced-stage PD. Vitamin D status is related not only to bone mass, but also to muscle function. Muscular weakness and hypotonia are symptoms related to rickets and osteomalacia, and recent studies suggest that one of the effects of vitamin D is muscular function improvement [15]. Low serum levels of 25 hydroxyvitamin D (25 OHD) have been reported previously in PD patients [7,16]. Body composition analysis by dual-energy X-ray absorptiometry (DXA) provides information on total body fat mass, lean mass, bone mineral content (BMC), and BMD. Studies on body composition of PD patients using DXA are scanty [14,17], and their results differ.
ARTICLE IN PRESS 356
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The aim of the present study was to compare body composition, as determined by DXA, of PD patients with age- and gender-matched controls, and to determine possible associations among body composition parameters, bone mass, and biochemical determinations of mineral metabolism.
2. Methods 2.1. Patients and controls Thirty-eight consecutive PD patients seen at the outpatients clinic of the PD and movement disorder program of the Hospital de Clı´ nicas were asked to participate in this study. Twenty-two met the following inclusion criteria: absence of any concomitant disease or medication known to affect bone and mineral metabolism, absence of malignancy, and no alcohol or drug abuse. The control group comprised 104 subjects aged 50–79 years, with no history of fractures or any concomitant disease or medication known to affect bone or mineral metabolism, who agreed to participate in this protocol. The protocol was approved by the Ethics Committee of the Hospital de Clı´ nicas, and written informed consent was given by patients and controls before the onset of the study.
3. Results We report the results obtained in 22 PD patients (12 women and 10 men) with a mean age of (X7SD) 67.376.8 years (range: 57–79 years). According to Hoehn and Yahr’s scale, 3 patients were at stage I, 8 at stage II, 10 at stage III, and 1 at stage IV of the disease. Mean illness duration was similar in women and men (6.773.9 vs. 6.675.6 years, respectively). Twenty-one patients were on levodopa, either as a monotherapy or associated to dopamine agonists. Only 1 patient was on a dopamine agonist alone. In addition, 1 patient was receiving quetiapine, and one was being treated with sertraline. Twelve patients had motor oscillations and peak-dose dyskinesias. Nine patients (41%) had suffered at least 1 fracture (5 men and 4 women). Six of them reported lower extremity long bone fractures (hip, tibiae, fibulae, metatarsal bones) and 3 reported fractures in other bones, including the ankle, heel, ribs, and carpal and metacarpal bones. X-ray studies served to detect a vertebral fracture in three patients. A total 16 fractures were recorded, 15 of which were reported to have been caused by a fall. 3.1. Body composition
2.2. Body composition analysis Whole-body DXA scanning was performed in PD patients and controls in order to analyze body composition. Total body fat mass, lean mass, BMC, and BMD were determined. To minimize inter-observer variation, the same technical expert, who could not be blinded due to clinical evidences of PD, performed all the analyses. Anthropometric measurements were made using standardized techniques.
To increase the accuracy of our results, a subgroup of age and sex-matched control subjects served to establish absolute mean comparisons (n ¼ 88, 44 women and 44 men). Anthropometric and body composition data of PD patients and controls are shown in Table 1. Women with PD were found to have significantly lower weight (9.5%), BMI (9.2%), fat mass (24.0%), and BMD (5.6%) than controls.
2.3. Biochemical determinations
3.2. Biochemical parameters of bone metabolism
Fasting blood and 24-h urine samples were collected from all the patients. The serum and urine samples were frozen and stored until processed. Serum calcium, phosphate, total alkaline phosphatase (AP), urinary calcium, and creatinine determinations were performed using standard techniques. Bone alkaline phosphatase (BAP) was determined by agglutination with wheat germ [18]. Serum levels of 25OHD were determined by radioimmunoassay (DIASORIN). Inter- and intra-assay coefficients of variation (CV) were 19% and 7.6%, respectively. All samples for 25OHD, AP, and BAP determinations were analyzed in the same assay and processed simultaneously in order to minimize interassay variation.
Table 2 shows mean values of biochemical determinations performed in PD patients. Serum levels of calcium, phosphorus, AP, and BAP were in the normal range in all patients. The limit of insufficiency was defined at 25OHD levels o20 ng/ml, in keeping with McKenna and Freaney [19]. Levels of 25 OHD were below 20 ng/ml in 14 subjects (64%). In addition, women with PD had lower 25OHD levels than men patients (15.276.1 vs. 23.679.3 ng/ml, respectively, po0.05).
2.4. Statistical analysis Statistical analysis was performed using the SPSS statistical software package (SPSS Inc., Chicago, IL). Comparisons between PD patients and controls were evaluated using a non-parametric unpaired test (Mann–Whitney). Linear associations in the PD patient group were analyzed using Spearman’s correlation coefficients. A value of po0.05 was considered significant.
3.3. Correlations in PD patients Levels of 25OHD correlated positively with BMC (r: 0.43, po0.05) and negatively with AP levels (r: 0.44, po0.05). BMD correlated positively with BMC (r: 0.94, po0.001), fat mass (r: 0.44, po0.05), and lean mass (r: 0.72, po0.001). BMI correlated positively with BMD (r: 0.60, po0.01), BMC (r: 0.52, po0.02), and fat mass (r: 0.87, po0.001), and negatively with illness duration (r: 0.43, po0.05). However, no correlation was observed
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Table 1 Anthropometric and body composition data of Parkinson’s disease patients and sex and age matched controls Women
AGE (years) WEIGHT (kg) HEIGHT (m) BMI (kg/m2) BMD (g/cm2) BMC (g) LM (g) FM (g)
Men
Controls (n ¼ 44) X7SD (range)
PD patients (n ¼ 12)
Controls (n ¼ 44)
PD patients (n ¼ 10)
66.476.3 (58.0–77.0) 62.976.7 (47.0–74.1) 1.5570.06 (1.46–1.67) 26.172.4 (20.8–30.0) 1.01870.065 20247259 3706072862 2422874977
67.377.2 (57–78) 56.9711.1 (43.3–57.0) 1.5570.07 (1.43–1.70) 23.774.9 (16.7–32.5) 0.95870.109 18767378 3625773669 1842279742
67.176.0 (57–79) 74.378.3 (58.4–89.7) 1.7070.06 (1.54–1.86) 25.872.3 (21.0–29.6) 1.19670.073 28797347 5202975352 1943074944
67.476.7 (58–75) 74.076.4 (61.7–81.0) 1.6970.05 (1.63–1.80) 25.472.0 (22.2–28.0) 1.17670.124 28827411 5191273189 1811174747
PD, Parkinson’s disease; BMI, body mass index; BMD, bone mineral density; BMC, bone mineral content; LM, lean mass; FM, fat mass. po0.05 vs. controls.
Table 2 Biochemical parameters of bone metabolism in patients with Parkinson’s disease
Serum calcium (mg/dl) Serum phosphorus (mg/dl) Alkaline phosphatase (IU/l) Bone alkaline phosphatase (IU/l) 25 OHD (ng/ml)
X (SD)
Reference range
9.6 3.5 145.9 75.1 19.0
8.9–10.4 2.6–4.4 68–240 31–95 Insufficiencyo20
(0.3) (0.3) (44.8) (13.8) (8.6)
between BMI and lean mass. No correlations were found between the H–Y stages and any of the studied variables. 4. Discussion According to our results, female PD patients were found to exhibit lower weight, BMI, and fat mass as determined by DXA than their corresponding healthy controls. These results are in agreement with previous anthropometric studies reporting PD patients to be at greater nutritional risk than controls, presenting decreased BMI, decreased body fat, and weight loss even when calorie intake is high [10–13,20,21]. To our knowledge, only two previous studies used DXA to evaluate body composition in PD patients; however, neither of them analyzed bone or mineral metabolism. Toth et al. [17] failed to find differences in fat mass and percentage fat mass between elderly PD patients and control subjects; this could be due to the small size of both patient and control samples. Petroni et al. [14] found PD patients to have an excess of fat tissue and a decrease in lean body mass (sarcopenic obesity); however, the authors failed to compare results with values corresponding to age matched healthy subjects. In our group of PD patients, BMI was found to correlate positively with fat mass, BMD and BMC, and negatively with illness duration, but no correlations were found between lean mass and BMI. In addition, no differences in lean mass were observed between PD patients and controls. A significant decrease in BMD was observed in female
patients. It is well documented that body composition components, including fat mass, influence bone mass [22,23]. Therefore, our findings suggest that, in this group of women with PD, low fat mass could be a contributing factor to their decreased BMD. Many authors have described a high incidence of low BMD in PD patients [2,4,5,16,24–27], and the strong correlation between low bone density and the risk of fragility fractures is well established [28]. The risk of new vertebral fractures increases by a factor of 2.0–2.4 for each standard deviation decrease in bone density, irrespective of the site of bone density measurement, and similar results have been found for hip and other non-vertebral fractures [28]. Increased fracture rate has been reported previously in PD patients [1–3]; likewise, the group of PD patients studied herein showed an elevated number of fractures. Decreased BMD in PD patients has been related to vitamin D deficiency and immobilization [7]. Low levels of 25 OHD are related to low BMD [29]. In agreement with previously published data [30,31] the women studied herein presented lower 25 OHD levels than the men. It must be pointed out that although the male PD patients did not exhibit a decrease in BMD or differences in body composition compared with their matched controls, the number of fractured patients and of total fractures was similar in men and women. Given that the duration and severity of the disease was similar in both groups, it can be posited that the fractures in the group of male PD patients were caused mainly by falls or other factors affecting bone quality that were not evaluated in this study. Taking into account that vitamin D status has been found to be associated with muscular function [15] and that falls in PD patients are caused in part by postural instability and commonly occur during transfer, such as rising from a chair or lying down in bed [8,32], low serum levels of 25 OHD could aggravate instability, thus increasing the inherent risk of falls in these patients. In conclusion, the results obtained in this group of PD patients suggest that low fat mass and reduced levels of 25 OHD in women could be contributing factors to the observed decrease in BMD and, consequently, to the high
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number of fractures. It is also possible that the reported decreased levels of 25 OHD increased the risk of falls, leading to the increased number of fractures observed in the group of male PD patients. It must be pointed out that the present study was conducted on a small sample of patients. Further studies using larger samples should be performed. In view of recent findings reported in the literature and the data presented herein, we suggest considering routine assessment of body composition and mineral metabolism of PD patients. Administration of vitamin D supplement to PD patients presenting low 25 OHD levels is recommended. Acknowledgments This study was partially supported by the Fundacio´n de Osteopororsis y Enfermedades Metabo´licas y Oseas (FOEMO) and the Consejo Nacional de Investigaciones Cientı´ ficas y Tecnolo´gicas (CONICET) of Argentina. References [1] Johnell O, Melton III LJ, Atkinson EJ, O’Fallon WM, Kurland LT. Fracture risk in patients with parkinsonism: a population-based study in Olmsted County, Minnesota. Age Ageing 1992;21:32–8. [2] Sato Y, Kaji M, Tsuru T, Oizumi K. Risk factors for hip fractures among elderly patients with Parkinson’s disease. J Neurol Sci 2001;182:89–93. [3] Genever RW, Downes TW, Medcalf P. Fracture rates in Parkinson’s disease compared with age- and gender-matched controls: a retrospective cohort study. Age Aging 2005;34:21–4. [4] Aita JF. Why patients with Parkinson’s disease fall. JAMA 1982;247:515–6. [5] Sato Y, Manabe S, Kuno H, Oizumi K. Amelioration of osteopenia and Hypovitaminosis D by 1alpha-hydroxivitamin D3 in elderly patients with parkinson’s disease. J Neurol Neurosurg Psychiatry 1999;66:64–8. [6] Wood BH, Bilclough JA, Bowron A, Walker RW. Incidence and prediction of falls in Parkinson’s disease: a prospective multidisciplinary study. J Neurol Neurosurg Psychiatry 2002;72:721–5. [7] Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology 1997;49:1273–8. [8] Grimbergen YAM, Munneke M, Bastiaan RB. Falls in Parkinson’s disease. Curr Opin Neurol 2004;17:405–15. [9] Bloem BR, Bhatia KP. Gait and balance in basal ganglia disorders. In: Bronstein AM, Brandt T, Nutt JG, Woollacott MH, editors. Clinical disorders of balance, posture and gait. London: Arnold; 2004. p. 173–206. [10] Durrieu G, Llau ME, Rascol O, Senard JM, Rascol A, Montastruc JL. Parkinson’s disease and weight loss: a study with anthropometric and nutritional assessment. Clin Auton Res 1992;2:153–7. [11] Markus HS, Tomkins AM, Stern GM. Increased prevalence of undernutrition in Parkinson’s disease and its relationship to clinical disease parameters. J Neural Transm Park Dis Dement Sect 1993;5:117–25.
[12] Beyer PL, Palarino MY, Michalek D, Busenbark K, Koller WC. Weight change and body composition in patients with Parkinson’s disease. J Am Diet Assoc 1995;95:979–83. [13] Cheshire W, Zbigniew KW. Body mass index is reduced early in Parkinson’s disease. Parkinsomism Rel Dis 2005;11:35–8. [14] Petroni ML, Albani G, Bicchiega V, et al. Body composition in advanced-stage Parkinson’s disease. Acta Diabetol 2003;40:S187–90. [15] Pfeifer M, Begerow B, Minne HW. Vitamin D and muscle function. Osteoporosis Int 2002;13:187–94. [16] Sato Y, Masahide K, Tsuru T, Satoh K, Kondo I. Vitamin K deficiency and osteopenia in vitamin D-deficient elderly women with Parkinson’s disease. Arch Phys Med Rehabil 2002;83:86–91. [17] Toth MJ, Fishman PS, Poehlman ET. Free-living daily energy expenditure in patients with Parkinson’s disease. Neurology 1997;48:88–91. [18] Farley JR, Hall SL, Ilacas D, Orcutt C, Miller BE, Hill CS, et al. Quantification of skeletal alkaline phosphatase in osteoporotic serum by wheat germ agglutinin precipitation, heat inactivation, and a twosite immunoradiomeric assay. Clin Chem 1994;40:1749–56. [19] Mc Kenna MJ, Freaney R. Secondary hyperparathyroidism in the elderly: means to defining hypovitaminosis D. Osteoporos Int 1998;8(Suppl 2):3–6. [20] Davies KN, King D, Davies H. A study of the nutritional status of elderly patients with Parkinson’s disease. Age Aging 1994;23:142–5. [21] Lorefalt B, Ganowiak W, Phalhagen S, Toss G, Unosson M, Granerus AK. Factors of importance for weight loss in elderly patients with Parkinson’s disease. Acta Neurol Scand 2004;110: 180–7. [22] Makovey J, Naganathan V, Sambrook P. Gender differences in relationships between body composition components, their distribution and bone mineral density: a cross-sectional opposite sex twin study. Osteoporosis Int 2005;16:1495–505. [23] Mautalen C, Bagur A, Vega E, Gonzalez D. Body composition in normal and osteoporotic women. Medicina (Buenos Aires) 1996;56:29–34. [24] Ishizaki F, Harada T, Katayama S, Abe H, Nakamura S. Relationship between osteopenia and clinical characteristics of Parkinson’s disease. Mov Disord 1993;8:507–11. [25] Kao CH, Chen CC, Wang SJ, Chia LG, Yeh SH. Bone mineral density in patients with Parkinson’s disease measured by dual photon absorptiometry. Nucl Med Commun 1994;15:173–7. [26] Taggart H, Crawford V. Reduced bone density of the hip in elderly patients with Parkinon’s disease. Age Aging 1995;24:326–8. [27] Revilla M, de la Sierra G, Aguado F, Varela L, Jiminez-Jimenez FJ, Rico H. Bone mass in Parkinson’s disease: a study with three methods. Calc Tissue Int 1996;58:311–5. [28] Wasnich R. Bone mass measurement: prediction risk. Am J Med 1993;95(5A):6S–10S. [29] Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Abnormal bone and calcium metabolism in immobilized Parkinson’s disease patients. Mov Disord 2005;20:1598–603. [30] Oliveri B, Plantalech L, Bagur A, Wittich AC, Rovai G, Lo´pez Giocanelli J, et al. High prevalence of vitamin D insufficiancy in healthy elderly people living at home in Argentina. Eur J Clin Nut 2004;58:337–42. [31] van der Wielsen RP, Lowl MRH, van der Berg H, de Groot L, Haller J, Moreiras O, et al. Serum 25 OHD concentration among elderly people in Europe. Lancet 1995;346:207–10. [32] Stack E, Ashburn A. Falls events described by people with Parkinson’s disease: implications for clinical interviewing and the research agenda. Physiother Res Int 1999;4:190–200.
Parkinsonism and Related Disorders 13 (2007) 355–358 www.elsevier.com/locate/parkreldis
A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson’s disease Marı´ a C. Ferna´ndeza, Muriel S. Parisia,b,, Sergio P. Dı´ azc, Silvina R. Mastagliaa,b, Juan M. Deferraria, Mariana Seijoa, Alicia Bagura, Federico Michelic, Beatriz Oliveria,b a
Department of Internal Medicine, Seccio´n Osteopatı´as Me´dicas, Hospital de Clı´nicas, Universidad de Buenos Aires, Co´rdoba 2351, 8 piso, (1120) Buenos Aires, Argentina b Researcher of the Consejo Nacional de Investigaciones Cientı´ficas y Tecnolo´gicas (CONICET), Argentina c Programa de Parkinson y Movimientos Anormales del Instituto de Neurociencias Aplicadas, Hospital de Clı´nicas, Universidad de Buenos Aires, Argentina Received 12 August 2006; received in revised form 30 November 2006; accepted 6 December 2006
Abstract The impact of body composition on bone and mineral metabolism in Parkinson’s disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (po0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels. r 2007 Elsevier Ltd. All rights reserved. Keywords: Parkinson’s disease; Vitamin D; Body composition; Bone mineral density
1. Introduction Patients with Parkinson’s disease (PD) are known to be at higher risk of fractures than healthy subjects [1–3]. Cumulative evidence indicates that this is related to several contributing factors, including increased rate of falls, reduced bone mineral density (BMD), reduced body mass index (BMI), and vitamin D deficiency [2,4–7]. Falls in PD are caused by many independent, albeit often coexistent, mechanisms such as postural instability, difficulty with transfer, gait disturbances and orthostatic syncope [8]. Consequently, fear of renewed falls may lead to a self-imposed restriction of daily activities causing immobility, which in turn is associated with osteoporosis and reduced fitness [9]. Corresponding author. Department of Internal Medicine, Seccio´n Osteopatı´ as Me´dicas, Hospital de Clı´ nicas, Universidad de Buenos Aires, Co´rdoba 2351, 8 piso (1120) Buenos Aires-Argentina. Tel.: 54 11 59508972; fax: 54 11 59508973. E-mail address: [email protected] (M.S. Parisi).
1353-8020/$ - see front matter r 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2006.12.010
There are reports indicating that PD patients are at greater nutritional risk [10–12], and a recent study by Cheshire and Zbigniew [13] reported that reduced BMI is observed early in the course of the disease. Both the symptoms of the disease and medication side effects can limit food intake. Motor impairment secondary to PD itself can also affect body composition. Petroni et al. [14] described the presence of sarcopenic obesity, defined as an excess of fat tissue and a decrease in lean body mass, in advanced-stage PD. Vitamin D status is related not only to bone mass, but also to muscle function. Muscular weakness and hypotonia are symptoms related to rickets and osteomalacia, and recent studies suggest that one of the effects of vitamin D is muscular function improvement [15]. Low serum levels of 25 hydroxyvitamin D (25 OHD) have been reported previously in PD patients [7,16]. Body composition analysis by dual-energy X-ray absorptiometry (DXA) provides information on total body fat mass, lean mass, bone mineral content (BMC), and BMD. Studies on body composition of PD patients using DXA are scanty [14,17], and their results differ.
ARTICLE IN PRESS 356
M.C. Ferna´ndez et al. / Parkinsonism and Related Disorders 13 (2007) 355–358
The aim of the present study was to compare body composition, as determined by DXA, of PD patients with age- and gender-matched controls, and to determine possible associations among body composition parameters, bone mass, and biochemical determinations of mineral metabolism.
2. Methods 2.1. Patients and controls Thirty-eight consecutive PD patients seen at the outpatients clinic of the PD and movement disorder program of the Hospital de Clı´ nicas were asked to participate in this study. Twenty-two met the following inclusion criteria: absence of any concomitant disease or medication known to affect bone and mineral metabolism, absence of malignancy, and no alcohol or drug abuse. The control group comprised 104 subjects aged 50–79 years, with no history of fractures or any concomitant disease or medication known to affect bone or mineral metabolism, who agreed to participate in this protocol. The protocol was approved by the Ethics Committee of the Hospital de Clı´ nicas, and written informed consent was given by patients and controls before the onset of the study.
3. Results We report the results obtained in 22 PD patients (12 women and 10 men) with a mean age of (X7SD) 67.376.8 years (range: 57–79 years). According to Hoehn and Yahr’s scale, 3 patients were at stage I, 8 at stage II, 10 at stage III, and 1 at stage IV of the disease. Mean illness duration was similar in women and men (6.773.9 vs. 6.675.6 years, respectively). Twenty-one patients were on levodopa, either as a monotherapy or associated to dopamine agonists. Only 1 patient was on a dopamine agonist alone. In addition, 1 patient was receiving quetiapine, and one was being treated with sertraline. Twelve patients had motor oscillations and peak-dose dyskinesias. Nine patients (41%) had suffered at least 1 fracture (5 men and 4 women). Six of them reported lower extremity long bone fractures (hip, tibiae, fibulae, metatarsal bones) and 3 reported fractures in other bones, including the ankle, heel, ribs, and carpal and metacarpal bones. X-ray studies served to detect a vertebral fracture in three patients. A total 16 fractures were recorded, 15 of which were reported to have been caused by a fall. 3.1. Body composition
2.2. Body composition analysis Whole-body DXA scanning was performed in PD patients and controls in order to analyze body composition. Total body fat mass, lean mass, BMC, and BMD were determined. To minimize inter-observer variation, the same technical expert, who could not be blinded due to clinical evidences of PD, performed all the analyses. Anthropometric measurements were made using standardized techniques.
To increase the accuracy of our results, a subgroup of age and sex-matched control subjects served to establish absolute mean comparisons (n ¼ 88, 44 women and 44 men). Anthropometric and body composition data of PD patients and controls are shown in Table 1. Women with PD were found to have significantly lower weight (9.5%), BMI (9.2%), fat mass (24.0%), and BMD (5.6%) than controls.
2.3. Biochemical determinations
3.2. Biochemical parameters of bone metabolism
Fasting blood and 24-h urine samples were collected from all the patients. The serum and urine samples were frozen and stored until processed. Serum calcium, phosphate, total alkaline phosphatase (AP), urinary calcium, and creatinine determinations were performed using standard techniques. Bone alkaline phosphatase (BAP) was determined by agglutination with wheat germ [18]. Serum levels of 25OHD were determined by radioimmunoassay (DIASORIN). Inter- and intra-assay coefficients of variation (CV) were 19% and 7.6%, respectively. All samples for 25OHD, AP, and BAP determinations were analyzed in the same assay and processed simultaneously in order to minimize interassay variation.
Table 2 shows mean values of biochemical determinations performed in PD patients. Serum levels of calcium, phosphorus, AP, and BAP were in the normal range in all patients. The limit of insufficiency was defined at 25OHD levels o20 ng/ml, in keeping with McKenna and Freaney [19]. Levels of 25 OHD were below 20 ng/ml in 14 subjects (64%). In addition, women with PD had lower 25OHD levels than men patients (15.276.1 vs. 23.679.3 ng/ml, respectively, po0.05).
2.4. Statistical analysis Statistical analysis was performed using the SPSS statistical software package (SPSS Inc., Chicago, IL). Comparisons between PD patients and controls were evaluated using a non-parametric unpaired test (Mann–Whitney). Linear associations in the PD patient group were analyzed using Spearman’s correlation coefficients. A value of po0.05 was considered significant.
3.3. Correlations in PD patients Levels of 25OHD correlated positively with BMC (r: 0.43, po0.05) and negatively with AP levels (r: 0.44, po0.05). BMD correlated positively with BMC (r: 0.94, po0.001), fat mass (r: 0.44, po0.05), and lean mass (r: 0.72, po0.001). BMI correlated positively with BMD (r: 0.60, po0.01), BMC (r: 0.52, po0.02), and fat mass (r: 0.87, po0.001), and negatively with illness duration (r: 0.43, po0.05). However, no correlation was observed
ARTICLE IN PRESS M.C. Ferna´ndez et al. / Parkinsonism and Related Disorders 13 (2007) 355–358
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Table 1 Anthropometric and body composition data of Parkinson’s disease patients and sex and age matched controls Women
AGE (years) WEIGHT (kg) HEIGHT (m) BMI (kg/m2) BMD (g/cm2) BMC (g) LM (g) FM (g)
Men
Controls (n ¼ 44) X7SD (range)
PD patients (n ¼ 12)
Controls (n ¼ 44)
PD patients (n ¼ 10)
66.476.3 (58.0–77.0) 62.976.7 (47.0–74.1) 1.5570.06 (1.46–1.67) 26.172.4 (20.8–30.0) 1.01870.065 20247259 3706072862 2422874977
67.377.2 (57–78) 56.9711.1 (43.3–57.0) 1.5570.07 (1.43–1.70) 23.774.9 (16.7–32.5) 0.95870.109 18767378 3625773669 1842279742
67.176.0 (57–79) 74.378.3 (58.4–89.7) 1.7070.06 (1.54–1.86) 25.872.3 (21.0–29.6) 1.19670.073 28797347 5202975352 1943074944
67.476.7 (58–75) 74.076.4 (61.7–81.0) 1.6970.05 (1.63–1.80) 25.472.0 (22.2–28.0) 1.17670.124 28827411 5191273189 1811174747
PD, Parkinson’s disease; BMI, body mass index; BMD, bone mineral density; BMC, bone mineral content; LM, lean mass; FM, fat mass. po0.05 vs. controls.
Table 2 Biochemical parameters of bone metabolism in patients with Parkinson’s disease
Serum calcium (mg/dl) Serum phosphorus (mg/dl) Alkaline phosphatase (IU/l) Bone alkaline phosphatase (IU/l) 25 OHD (ng/ml)
X (SD)
Reference range
9.6 3.5 145.9 75.1 19.0
8.9–10.4 2.6–4.4 68–240 31–95 Insufficiencyo20
(0.3) (0.3) (44.8) (13.8) (8.6)
between BMI and lean mass. No correlations were found between the H–Y stages and any of the studied variables. 4. Discussion According to our results, female PD patients were found to exhibit lower weight, BMI, and fat mass as determined by DXA than their corresponding healthy controls. These results are in agreement with previous anthropometric studies reporting PD patients to be at greater nutritional risk than controls, presenting decreased BMI, decreased body fat, and weight loss even when calorie intake is high [10–13,20,21]. To our knowledge, only two previous studies used DXA to evaluate body composition in PD patients; however, neither of them analyzed bone or mineral metabolism. Toth et al. [17] failed to find differences in fat mass and percentage fat mass between elderly PD patients and control subjects; this could be due to the small size of both patient and control samples. Petroni et al. [14] found PD patients to have an excess of fat tissue and a decrease in lean body mass (sarcopenic obesity); however, the authors failed to compare results with values corresponding to age matched healthy subjects. In our group of PD patients, BMI was found to correlate positively with fat mass, BMD and BMC, and negatively with illness duration, but no correlations were found between lean mass and BMI. In addition, no differences in lean mass were observed between PD patients and controls. A significant decrease in BMD was observed in female
patients. It is well documented that body composition components, including fat mass, influence bone mass [22,23]. Therefore, our findings suggest that, in this group of women with PD, low fat mass could be a contributing factor to their decreased BMD. Many authors have described a high incidence of low BMD in PD patients [2,4,5,16,24–27], and the strong correlation between low bone density and the risk of fragility fractures is well established [28]. The risk of new vertebral fractures increases by a factor of 2.0–2.4 for each standard deviation decrease in bone density, irrespective of the site of bone density measurement, and similar results have been found for hip and other non-vertebral fractures [28]. Increased fracture rate has been reported previously in PD patients [1–3]; likewise, the group of PD patients studied herein showed an elevated number of fractures. Decreased BMD in PD patients has been related to vitamin D deficiency and immobilization [7]. Low levels of 25 OHD are related to low BMD [29]. In agreement with previously published data [30,31] the women studied herein presented lower 25 OHD levels than the men. It must be pointed out that although the male PD patients did not exhibit a decrease in BMD or differences in body composition compared with their matched controls, the number of fractured patients and of total fractures was similar in men and women. Given that the duration and severity of the disease was similar in both groups, it can be posited that the fractures in the group of male PD patients were caused mainly by falls or other factors affecting bone quality that were not evaluated in this study. Taking into account that vitamin D status has been found to be associated with muscular function [15] and that falls in PD patients are caused in part by postural instability and commonly occur during transfer, such as rising from a chair or lying down in bed [8,32], low serum levels of 25 OHD could aggravate instability, thus increasing the inherent risk of falls in these patients. In conclusion, the results obtained in this group of PD patients suggest that low fat mass and reduced levels of 25 OHD in women could be contributing factors to the observed decrease in BMD and, consequently, to the high
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