Therapeutic challenges in elderly patients with symptomatic hypercalcaemia caused by primary hyperparathyroidism.

BACKGROUND: Hypercalcaemia resulting from primary hyperparathyroidism (PHPT) can cause a wide range of symptoms, including cognitive disorders, psychiatric symptoms and muscle weakness. Parathyroid surgery is the only definite cure for PHPT. When surgery is contraindicated or patients decide against it, several non-surgical treatment options are available. OBJECTIVE: To illustrate the treatment options of symptomatic hypercalcaemia caused by PHPT in the elderly and discuss these options in consideration of the available evidence. DESIGN: Consecutive case series. SETTING: University hospital. PATIENTS: Four older patients aged 79-87 years with symptomatic hypercalcaemia resulting from PHPT. RESULTS: Three patients had a parathyroid adenoma shown on a sestamibi scan. Normocalcaemia and resolution of symptoms was achieved by different treatment scenarios encompassing forced saline hydration, forced diuresis, intravenous pamidronate and cinacalcet, a calcimimetic drug. In one patient, no parathyroid abnormalities were revealed with imaging. Treatment with cinacalcet resulted in normocalcaemia and a strong improvement of symptoms. CONCLUSION: In clinical practice, different treatment scenarios are chosen for the treatment of elderly patients with symptomatic hypercalcaemia caused by PHPT. The introduction of cinacalcet offers a new treatment paradigm. We propose to apply cinacalcet preceding elective surgery as an alternative option to standard therapy or as maintenance dose when surgery is not possible.

Use of anti-depressants and the risk of fracture of the hip or femur.

SUMMARY: Anti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients. INTRODUCTION: Anti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use. METHODS: A case-control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region. RESULTS: The risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (OR(adj)) 2.35 [95% confidence interval (CI) 1.94-2.84]) and TCAs (ORadj 1.76 [95% CI 1.45-2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from OR(adj) 1.64 [95% CI 1.14-2.35] for drugs with low 5-HTT inhibition to OR(adj) 2.31 [95% CI 1.94-2.76] for those with high 5-HTT inhibiting properties. CONCLUSION: Current use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

Postmenopausal HRT and tibolone in relation to muscle strength and body composition.

OBJECTIVES: Sarcopenia, the loss of muscle mass with age, has a great impact on physical function, and especially in postmenopausal women, who experience a greater decline in muscle strength than do men of similar age. Conventional hormone replacement therapy (HRT) may diminish this loss of muscle strength and may even increase muscle strength. However, HRT is not currently promoted for this indication because of its negative side effects, which is why tibolone, a synthetic steroid with oestrogenic, progestogenic, and androgenic activity, may be an alternative option. The aim of this article was to review data on the effect of HRT and tibolone on muscle strength and body composition in postmenopausal women. METHODS: Medline, Pubmed, Embase, and Sumsearch were searched for articles on the effect of HRT and tibolone on muscle strength and body composition, using the Mesh terms hormone replacement therapy and clinical trial combined with muscle strength or body composition. Tibolone was added as search term with clinical trial and muscle strength or body composition. RESULTS: Three of five randomized controlled trials reported a significant positive effect of HRT on muscle strength but not on body composition. Tibolone significantly increased handgrip strength and isometric knee extension strength in one randomized placebo-controlled, double-blind trial and increased mean knee extensor strength in one cross-sectional study. Tibolone also increased the lean body mass and decreased the accumulation of body fat. CONCLUSIONS: HRT and tibolone increase muscle strength. Unlike HRT, tibolone also increases lean body mass and significantly reduces the total body fat content. Further research is recommended to determine whether tibolone is a safe treatment for sarcopenia.

Diagnostic errors; the need to have autopsies.

INTRODUCTION: In geriatric patients, atypical presentation and limitations in diagnostic scope may lead to underdiagnosis. The aim of this study was to establish the frequency, nature and causes of clinical diagnostic errors in a geriatric population. DESIGN: A retrospective study. METHODS: We assessed the accuracy of clinical diagnosis using autopsy results as our gold standard. Factors likely to influence accuracy of clinical diagnosis were identified. We used the (modified) classification of Goldman et al. to define discrepancy. RESULTS: We analysed 93 autopsies of a total of 331 deaths (28%). Discrepancies in major diagnoses were seen in 36 cases (39%). In 17 of these, clinical management might have been different if the diagnosis had been made premortem. These were: pulmonary embolism (4); unrecognised infection (4); intestinal ischaemia (3); ruptured aortic aneurysm (2); malignancy (1); tracheal obstruction (1); intestinal obstruction (1) and acute pancreatitis (1). Discrepancies in minor diagnoses were seen in 46 cases (50%). About one third of these were clinically relevant. Discrepancies occurred more frequently if there was a degree of uncertainty about clinical diagnosis p<0.001). CONCLUSION: Major discrepancies between clinical diagnosis and autopsy findings were seen in 39% of our study population. They occur more often in the case of uncertain clinical diagnosis. Our findings stress the continuing and important role of autopsy in improving clinical practice in geriatric medicine.

The assessment of body sway and the choice of the stability parameter(s).

This methodological study aims at comparison of the practical usefulness of several parameters of body sway derived from recordings of the center of pressure (CoP) with the aid of a static force platform as proposed in the literature. These included: mean displacement velocity, maximal range of movement along x- and y-co-ordinates, movement area, planar deviation, phase plane parameter of Riley and the parameters of the diffusion stabilogram according to Collins. They were compared in over 850 experiments in a group of young healthy subjects (n = 10, age 21-45 years), a group of elderly healthy (n = 38, age 61-78 years) and two groups of elderly subjects (n = 10 and n = 21, age 65-89 years) with stability problems under different conditions known to interfere with stability as compared to standing with open eyes fixing a visual anchoring point: closing the eyes, standing on plastic foam in stead of a firm surface and performing a cognitive task: the modified stroop test. A force platform (Kistler) was used and co-ordinates of the body's center of pressure were recorded during 60 s of quiet barefoot standing with a sampling frequency of 10 Hz. In general, the results show important overlapping among groups and test conditions. Mean displacement velocity shows the most consistent differences between test situations, health conditions and age ranges, but is not affected by an extra cognitive task in healthy old people. Mean maximal sideways sway range is different among groups and test conditions except for the cognitive task in young and elderly subjects. Standardised displacement parameters such as standard deviations of displacements and planar deviation discriminate less well than the actual range of motion or the velocity. The critical time interval derived from the diffusion stabilogram according to Collins et al. seems to add a specific type of information since it shows significant influence from addition of a cognitive task in old subjects standing on a firm surface but not when standing on plastic foam. The critical time interval shows no consistent relation to any other parameter. The influence of cognitive activity on balance merits further exploration. A new parameter, sum of maximal deviation time (SDT) was proposed showing complete discrimination between frail elderly and other old subjects when obtained while visual input was suppressed. It was concluded that mean displacement velocity seems to be the most informative parameter in most situations.

Axial and rotational alignment of the leg.

The axial and rotational alignments of the lower extremity are commonly referenced independently, with minimal research on whether coexistent axial and rotational malalignment cause pathologies. The present study analyzed whether a correlation exists between the axial and rotational alignments of the leg. The methodology to measure both alignments was adapted for computer tomography. Fifty patients were analyzed at five reference images to determine axial and rotational alignment. The reference images included the femoral head, the femoral shaft (at the level of the lesser trochanter), the distal femur, the proximal tibia, and the ankle joint. Axial alignment was calculated by using horizontal and vertical measurements of the location of the femoral head, the distal femur, and the ankle joint. Rotational alignments of femur, knee, and tibia were calculated using four angles: proximal femoral, distal femoral, proximal tibial, and ankle joint angles defined relative to a fixed reference. Pearson correlation analysis between axial alignment and the three mentioned rotational alignments were calculated. The correlation coefficient values ranged between -0.15-0.07 when comparing axial to rotational alignment, indicating that a week correlation exists between the two alignments. Though these results were derived using highly reproducible methods, the hypothesis of an existing correlation between the axial and rotational alignments of the leg was rejected. These findings allow for an improved understanding of lower extremity mechanics, which merit importance when considering pathologies of the leg and the surgical techniques that could ultimately benefit patients suffering from these pathologies.

[Tuberculosis spondylodiscitis in three older patients]. / Spondylodiscitis door tuberculose bij 3 oudere patiënten.

Three patients, two women aged 78 and 70 years, respectively, and a man aged 71 years, had back pain for months. Fever was absent. Blood parameters of infection were slightly or highly elevated. The diagnosis of spondylodiscitis was confirmed by MRI in all three patients. In one patient tuberculosis was confirmed by culture. One patient was from Turkey and the other two patients had been exposed professionally to tuberculosis. On two occasions, spondylodiscitis was complicated by compression of the spinal cord, and surgical intervention was necessary on one occasion because of neurological deficit. Initial treatment consisted of long-term bed rest and antituberculous therapy. All three patients recovered successfully. Tuberculous spondylodiscitis is a rare cause of back pain, but should be included in the differential diagnosis, particularly if there is an increased risk based on the medical history or if the patient comes from an endemic region or has an increased risk due to his or her profession.

[Cognitive deterioration in elderly due to primary hyperparathyroidism--resolved by parathyroidectomy]. / Cognitief verval bij ouderen door primaire hyperparathyreoïdie--opgelost door parathyreoïdectomie.

Three patients, two women aged 79 and 80 and a man aged 84, showed symptoms of cognitive impairment caused by primary hyperparathyroidism. Parathyroidectomy lead to a marked improvement in the symptoms. The incidence of primary hyperparathyroidism increases with age. Most patients only show slight symptoms. In addition, clinical symptoms in elderly patients differ from those in younger patients with mental changes, general tiredness and reduced muscular strength being prevalent. In accordance with the literature, which shows high cure rates with low morbidity and mortality, we recommend that parathyroid surgery be considered in elderly patients who exhibit only slight or mental symptoms of primary hyperparathyroidism.

The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women.

Changes in body composition occur around the menopausal transition. The major characteristics are a decline in fat-free mass and an increase in body fat as a percentage of body weight. These alterations might be affected by age only or by menopause-related changes in hormone concentration. In this study the effects of tibolone, a tissue-specific compound with favorable effects on bone, vagina, and climacteric symptoms, were determined on body composition using bioelectrical impedance analysis. The focus was especially on fat mass, fat-free mass, and total body water in a group of 85 healthy women (mean +/- SD age, 54.2 +/- 4.7 yr), between 1-15 yr postmenopausal. Participants were randomly assigned to either tibolone (2.5 mg; n = 42) or identically appearing placebo tablets (n = 43) daily for 12 months. All analyses were based on the intent to treat group and last visit. Compared with placebo, tibolone significantly increased fat-free mass by 0.85 kg (P = 0.003) and total body water by 0.78 liter (P = 0.001). No significant difference was observed on the fat mass parameter (P = 0.16). From these results it can be concluded that tibolone may counteract the postmenopausal changes in body composition.

Relationship between circulating levels of sex hormones and insulin-like growth factor-1 and fluid intelligence in older men.

The relationship was investigated between baseline serum levels of total testosterone (T), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), ESTRADIOL (E2), sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1) and cognitive functioning in 25 healthy older men (mean age 69.1 years). Cognitive tests concerned measures not sensitive to ageing (crystallized intelligence), and measures sensitive to ageing (fluid intelligence and verbal long-term memory). Partial correlation coefficients (controlled for level of education) revealed significant associations of total T (r = -.52, p = -.009), SHBG (r - .59, p = .002) and IGF-1 (r = .54, p = .007) with the composite measure of fluid intelligence test performance, but not with crystallized intelligence, nor verbal long-term memory. Stepwise hierarchical regression analysis with the composite measure of fluid intelligence as the dependent variable showed that the contributions of SHBG, total T, and IGF-1 were not additive.

Quick titration of pergolide in cotreatment with domperidone is safe and effective.

The purpose of the study was to analyze efficacy and safety of quick pergolide titration combined with domperidone. In an open-label prospective study, pergolide was titrated in 16 days to a maximum of 3 mg/d doses as adjunctive treatment to L-Dopa in 10 elderly patients with Parkinson's disease. Sixty milligrams domperidone was started 2 days before and and continued during the pergolide titration period to prevent side effects. Adverse events were studied for 6 weeks. Efficacy was measured with the motor part ("on" condition) of the Unified Parkinson's Disease Rating Scale (UPDRS), the 2-minute walking test, the Timed Up and Go test, and the Postural-Locomotor-Manual test. After quick titration of pergolide with domperidone cotreatment, no symptomatic side effects were seen except for lightheadedness in one patient, which disappeared after dose reduction. The UPDRS motor score improved significantly from 21 +/- 8 at baseline to 16 +/- 7 and 12 +/- 7 after 1 and 2 weeks, respectively. The 2-minute walking distance improved significantly from 123 +/- 36 m at baseline to 136 +/- 41 m after 6 weeks. The Timed Up and Go and Postural-Locomotor-Manual test results, overall, did not show significant changes. Quick titration of pergolide to a maximum of 3 mg/d with domperidone cotreatment is safe and effective. Therefore, we recommend domperidone cotreatment in the titration period to prevent unnecessary failure of dopamine agonist treatment because of adverse effects.

Differences in gait parameters at a preferred walking speed in healthy subjects due to age, height and body weight.

The objective of our cross-sectional study was to investigate the changes associated with age and gender in walking speed, stride length and cadence of healthy women and men over the adult age range, and establish the effects of anthropometric indices such as height and body weight. We examined 118 women and 121 men (age range, 19-90 years). Subjects walked at their preferred speed over a 12-meter walkway crossing two Kistler force plates: cadence was calculated from heel strike times recorded from the Kistler force plates; walking speed was measured using an infrared reflecting system; and stride length was calculated from the walking speed and cadence. Older healthy subjects had lower values for walking speed and stride length than younger subjects. While there is little difference in the percentage reduction between women and men over the adult age range. the absolute values for walking speed are lower in women than men at all ages. In women, the percentage of explained variance for decline in walking speed was 30%, and for decline in stride length 400%. If body weight was also taken into account, the percentage of explained variance for walking speed was 37%, and for stride length 59%. A similar calculation for men yields 34% for decline in walking speed, and 42% for decline in stride length. Cadence was not associated with age, height and body weight. The standard errors for the estimates of walking speed in both women and men, respectively, are reduced by 8% and 3% using the multiple regression technique. The corresponding standard errors for stride length were reduced by, respectively, 19% and 13% if height in either sexes, or height and body weight in women, were taken into account. In conclusion, preferred walking speed and stride length decline with age in healthy people. Lower values found in old healthy subjects partly contributed to the difference in height and body weight between old and young subjects. Cadence was not correlated with age, height and body weight.

Evaluation of the applicability of HRT as a preservative of muscle strength in women.

OBJECTIVES: To review the studies that have been undertaken on the effects of postmenopausal hormone replacement therapy (HRT); especially oestrogen (+progestin) regimens on the preservation of muscle strength. Current knowledge of the mechanisms and actions of steroid- and sex hormones on skeletal muscle tissue will be used in an attempt to clarify the mechanism of action of a possible effect. The objective is to arrive at an agreement on whether or not postmenopausal oestrogen administration has a positive influence on skeletal muscle tissue. METHODS: Peer-reviewed publications were assessed. RESULTS: An age-related decrement in muscle strength can be found in both men and women. However, in women, an extra decline can be observed around the time of menopause. A possible relationship between the additional diminution in muscle strength and altered hormone concentrations after the onset of menopause has been suggested. Since women nowadays spend one-third of their life postmenopausal, it is extremely important to keep the decline in muscle mass as small as possible. Besides the continuation of a physically active lifestyle, HRT was suggested to serve as a protective mechanism. Although, the usefulness of HRT as a preservative of muscle strength appeared controversial. CONCLUSIONS: Skeletal muscle strength is sensitive to training up to a high age, though continuation of physical activity does not appear to protect skeletal muscles completely from age-related decrements. Therefore, the development of another preventive method would be useful. Considering the present knowledge it has all the hallmarks that HRT can be a useful tool in the maintenance of muscle strength in postmenopausal women. None the less, further research is necessary to endorse this theory.

Relationships between physical performance measures, age, height and body weight in healthy adults.

OBJECTIVE: we measured muscle strength and functional mobility in healthy men and women over the adult age range to investigate the changes with age and sex, and to establish the effects of the anthropometric indices height and weight. DESIGN: cross-sectional study. SUBJECTS AND METHODS: we recruited 74 healthy women (mean age 49.0, range 20-90) and 81 healthy men (mean age 51.6, range 20-90). We measured maximum isometric knee extension strength, handgrip strength and explosive leg extensor power. We assessed functional mobility quantitatively with the timed 'get up and go' test and the modified Cooper test. RESULTS: older subjects had lower values for muscle strength and muscle power than young subjects. Times for the timed 'get up and go' test were longer and distances in the modified Cooper test shorter. At about the age of 55, women showed an acceleration in the decline of isometric knee extension strength and handgrip strength (between 20 and 55 years, knee strength decreased by 10.3% and handgrip strength decreased by 8.2%, between 55 and 80 years the decreases were 40.2% and 28% respectively). Men showed a more gradual declines over the adult age range, with decreases in knee and handgrip strength of 24% and 19.6% between 20 and 55 years, and 23% and 17.4% between 55 and 80 years. The age-related decline is partly associated with differences in height and body weight. Women had higher correlations between muscle strength and functional mobility tests than men. CONCLUSIONS: muscle strength and functional mobility decline with age in healthy people; in women we observed an accelerated decrement in muscle strength above the age of 55. Lower values in healthy old subjects are partly associated with differences in height and body weight.

Age-sensitive cognitive function, growth hormone and insulin-like growth factor 1 plasma levels in healthy older men.

Circulating levels of growth hormone (GH) change during the process of aging. Decline of cognitive functioning with aging is also well established. In this study, we investigated whether insulin-like growth factor 1 (IGF-1) and the GH response to a challenge of GH-releasing hormone and GH-releasing peptide 6 were associated with age-sensitive cognitive functions, but not with functions that do not decline with aging, in 17 healthy male subjects aged between 66 and 76 years. In addition, relations with anthropometric measures were examined. Neuropsychological performance was scored on tests of variables not sensitive to aging (general knowledge, vocabulary, basic visual perception and reading ability), and of variables sensitive to aging (visuoconstructive ability, perceptual motor and mental processing speed, and verbal long-term memory). After correcting for education, the serum GH response was significantly associated with two age-sensitive cognitive tests (measures of mental processing speed), but with none of the tests not sensitive to aging. However, the direction of the association was opposite to the relation between IGF-1 and these cognitive tests: higher levels of GH response were associated with poorer cognitive performance, whereas higher levels of IGF-1 were associated with better performance. GH response, but not IGF-1, was inversely correlated with body mass index. The results are in accordance with previous research suggesting a disruption of the relation between IGF-1 and GH secretion in older age.

Muscle strength, functional mobility and vitamin D in older women.

Vitamin D deficiency may lead to loss of type II muscle fibres, and thereby to atrophy of proximal muscles with an increased risk of falling and bone fractures. The aim of the study was to determine if six months of vitamin D treatment (0.5 microg alphacalcidol) could positively influence values for muscle strength and functional mobility in vitamin D-deficient older women. Twenty-seven women entered the study which took place at a teaching hospital outpatient department. Ten vitamin D-deficient (serum 25(OH)D3 <20 nmol/L) older (>70 years) women and 13 age-matched female subjects with normal vitamin D levels (serum 25(OH)D3 >30 nmol/L) completed the study. Preand post-treatment data were obtained for isometric knee extensor strength, handgrip strength and functional mobility (walking distance over 2 minutes and the timed i'Up & Go" test). Six months of treatment with alphacalcidol led to significant improvements (compared to the controls) in values of isometric knee extensor strength (left leg: 14.6% +/- 5.7%. p=0.03; right leg: 11.5% +/- 5.0%, p=0.02) (mean +/- SEM). The achievements in the timed "Up & Go" test and 2-minute walking test did not improve in the alphacalcidol group compared to the controls after 6 months. However, within the vitamin D-deficient group, 6 months of alphacalcidol treatment led to a significant increase in the walking distance over 2 minutes (increase from 137.6 +/- 12.6 to 151.3 +/- 11.2 meters, p=0.03). The controls, with normal vitamin D levels, did not exhibit improvements in performance of any of the tests over a period of 6 months. Summarized, alphacalcidol seems to improve muscle strength and walking distance over 2 minutes in vitamin D-deficient older women.

Insulin-like growth factor-I and cognitive function in healthy older men.

The GH/insulin-like growth factor-I (GH/IGF-I) axis is known to be involved in aging of physiological functions. Recent studies indicate that the GH/IGF-I axis may be associated with cognitive functioning. The aim of the present study was to determine whether the age-related decline in circulating levels of IGF-I, as an index of anabolic status, is associated with cognitive functions that are known to decline with aging, but not with cognitive functions not sensitive to aging. Twenty five healthy older men with well-preserved functional ability participated in the study. We also administered neuropsychological tests of general knowledge, vocabulary, basic visual perception, reading ability, visuoconstructive ability, perceptual-motor speed, mental tracking, and verbal long-term memory. Performance on the last four tests decline with aging, whereas the first four of these tests have been shown not to be sensitive to cognitive aging. Mean age of the subjects was 69.1 +/- 3.4 (SD) yr (range 65-76 yr), their mean body mass index was 27.0 +/- 2.4 kg/m2, and their mean IGF-I level was 122 ng/mL (range: 50-220). We found IGF-I levels to be significantly associated with the performances (controlled for education) on the Digit Symbol Substitution test (r = 0.52, P = 0.009) and the Concept Shifting Task (r = -0.55, P = 0.005), which measure perceptual-motor and mental processing speed. Subjects with higher IGF-I levels performed better on these tests, performance on which is known to decline with aging. In conclusion, the results of this study support the hypothesis that circulating IGF-I may play a role in the age-related reduction of certain cognitive functions, specifically speed of information processing.

Spatial-temporal analysis of mobility over the adult age range using the Postural-Locomotor-Manual Test.

BACKGROUND: Mobility measurements were performed on healthy adult subjects to investigate changes over the adult age range and to obtain reference values. METHODS: Ninety-five males (19-90 years, mean 58.2) and 122 females (19-90 years, mean 51.8) were measured using the commercially available Postural-Locomotor-Manual Test (PLM-test). Subjects are required to perform a standard maneuver that is recorded using an optoelectronic technique. RESULTS: Older subjects carried out all phases of the maneuver more slowly than younger subjects. At about the age of 50 years, females showed a more rapid slowing down. Males showed a more gradual decrease over the adult age range. CONCLUSION: The PLM-test provides a fairly simple noninvasive method of assessing motor performance. However, it is important to separate male and female data in the determination of reference values.