Summary
Today, primary hyperparathyroidism (PHPT) in the developed countries is typically a disease with few or no obvious clinical symptoms. However, even in the asymptomatic cases the endogenous ...excess of PTH increases bone turnover leading to an insidious reversible loss of cortical and trabecular bone because of an expansion of the remodelling space and an irreversible loss of cortical bone due to increased endocortical resorption. In contrast trabecular bone structure and integrity to a large extent is maintained and there may be a slight periosteal expansion. Most studies have reported decreased bone mineral density (BMD) in PHPT mainly located at cortical sites, whereas sites rich in trabecular bone only show a modest reduction or even a slight increase in BMD. The frequent occurrence of vitamin D insufficiency and deficiency in PHPT and increased plasma FGF23 levels may also contribute to the decrease in BMD. The effect of smoking is unsolved. Epidemiological studies have shown that the relative risk of spine and nonspine fractures is increased in untreated PHPT starting up to 10 years before the diagnosis is made. Successful surgery for PHPT normalizes bone turnover, increases BMD and decreases fracture risk based on larger epidemiological studies. However, 10 years after surgery fracture risk appears to increase again due to an increase in forearm fractures.
There are no randomized controlled studies (RCTs) demonstrating a protective effect of medical treatment on fracture risk in PHPT. Less conclusive studies suggest that vitamin D supplementation may have a beneficial effect on plasma PTH and BMD in vitamin D deficient PHPT patients. Hormone replacement therapy (HRT) and maybe SERM appear to reduce bone turnover and increase BMD. However, their nonskeletal side‐effects preclude their use for this purpose. Bisphosphonates reduce bone turnover and increase BMD in PHPT as in osteoporosis and may be a therapeutical option in selected patients with low BMD. Obviously, there is a need for larger RCTs with fractures as end‐points that appraise this possibility. Calcimimetics reduce plasma calcium and PTH in PHPT but has no beneficial effect on bone turnover or BMD. In symptomatic hypercalcaemic PHPT with low BMD where curative surgery is impossible or contraindicated a combination of a calcimimetic and a bisphosphonate may be an undocumented therapeutical option that needs further evaluation.
Vitamin D and the elderly Mosekilde, Leif
Clinical endocrinology (Oxford),
March 2005, Letnik:
62, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
This review summarizes current knowledge on vitamin D status in the elderly with special attention to definition and prevalence of vitamin D insufficiency and deficiency, relationships ...between vitamin D status and various diseases common in the elderly, and the effects of intervention with vitamin D or vitamin D and calcium. Individual vitamin D status is usually estimated by measuring plasma 25‐hydroxyvitamin D (25OHD) levels. However, reference values from normal populations are not applicable for the definition of vitamin D insufficiency or deficiency. Instead vitamin D insufficiency is defined as the lowest threshold value for plasma 25OHD (around 50 nmol/l) that prevents secondary hyperparathyroidism, increased bone turnover, bone mineral loss, or seasonal variations in plasma PTH. Vitamin D deficiency is defined as values below 25 nmol/l. Using these definitions vitamin D deficiency is common among community‐dwelling elderly in the developed countries at higher latitudes and very common among institutionalized elderly, geriatric patients and patients with hip fractures. Vitamin D deficiency is an established risk factor for osteoporosis, falls and fractures. Clinical trials have demonstrated that 800 IU (20 µg) per day of vitamin D in combination with 1200 mg calcium effectively reduces the risk of falls and fractures in institutionalized patients. Furthermore, 400 IU (10 µg) per day in combination with 1000 mg calcium or 100 000 IU orally every fourth month without calcium reduces fracture risk in individuals over 65 years of age living at home. Yearly injections of vitamin D seem to have no effect on fracture risk probably because of reduced bioavailability. Simulation studies suggest that fortification of food cannot provide sufficient vitamin D to the elderly without exceeding present conventional safety levels for children. A combination of fortification and individual supplementation is proposed. It is argued that all official programmes should be evaluated scientifically. Epidemiological studies suggest that vitamin D insufficiency is related to a number of other disorders frequently observed among the elderly, such as breast, prostate and colon cancers, type 2 diabetes, and cardiovascular disorders including hypertension. However, apart from hypertension, causality has not been established through randomized intervention studies. It seems that 800 IU (20 µg) vitamin D per day in combination with calcium reduces systolic blood pressure in elderly women.
Summary
Objective
Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH, resulting ...in hypocalcaemia and hyperphosphataemia. Studies in patients with PHP are limited. We sought to identify all patients in Denmark with PHP and access their mortality data and risk of complications.
Design
Patients were identified through the Danish National Patient Registry and a prescription database, with subsequent validation by investigation of patient charts.
Methods
For each case, three age‐ (±2 years) and gender‐matched controls were randomly selected from the general background population. We identified a total of 60 cases, equal to a prevalence of 1·1/100 000 inhabitants. The average age at diagnosis was 13 years (range 1–62 years), and 42 were women. Only 14 patients had an identified mutation in the GNAS1 gene.
Results
Compared with controls, patients with PHP had an increased risk of neuropsychiatric disorders (P < 0·01), infections (P < 0·01), seizures (P < 0·01) and cataract (P < 0·01), whereas their risk of renal, cardiovascular, malignant disorders and fractures was compatible with the general background population. The same tendencies were found in a subgroup analysis in cases with genetically verified PHP.
Conclusion
Patients with PHP have an increased risk of neuropsychiatric disorders, infections, cataract and seizures, whereas mortality among PHP patients is compatible with that in the background population.
Context:
Renal complications in terms of hypercalciuria, nephrolithiasis, and nephrocalcinosis are well-known risks in primary hyperparathyroidism (PHPT) and may lead to impaired renal function.
...Evidence Acquisition:
We reviewed published evidence on the occurrence, pathophysiology, and consequences of renal complications in PHPT and highlighted areas of uncertainty that should be investigated further.
Evidence Synthesis:
In asymptomatic PHPT, renal stones are present in approximately 7% of the patients, which is a significantly higher prevalence than among patients without PHPT (1.6%). Also, before diagnosis of PHPT, risk of hospital admissions due to renal stones is increased compared with the background population, and the risk remains increased for at least 10 yr after surgical cure from PHPT. However, shortly after parathyroidectomy, risk of recurrent stone episodes is reduced to the recurrence rate among patients with idiopathic renal stone disease. In general, patients with PHPT who develop nephrolithiasis are of younger age and more often are males, compared with those who do not form renal calcifications. Although 24-h urinary calcium is decreased after parathyroidectomy, studies have shown a higher renal calcium excretion and lower serum phosphate levels in former PHPT patients compared with healthy controls, suggesting that these patients have some additional mineral disorder.
Conclusion:
All patients with a diagnosis of PHPT should initially be evaluated for renal calcifications by unenhanced helical computed tomography. If calcifications are present, parathyroidectomy is recommended. If symptoms develop after parathyroidectomy, patients should be evaluated and treated similar to other patients with renal stones.
Quantitative computed tomography (QCT), high-resolution peripheral QCT (HR-pQCT) and dual X-ray absorptiometry (DXA) scans are commonly used when assessing bone mass and structure in patients with ...osteoporosis. Depending on the imaging technique and measuring site, different information on bone quality is obtained. How well these techniques correlate when assessing central as well as distal skeletal sites has not been carefully assessed to date. One hundred and twenty-five post-menopausal women aged 56–82 (mean 63) years were studied using DXA scans (spine, hip, whole body and forearm), including trabecular bone score (TBS), QCT scans (spine and hip) and HR-pQCT scans (distal radius and tibia). Central site measurements of areal bone mineral density (aBMD) by DXA and volumetric BMD (vBMD) by QCT correlated significantly at the hip (
r
= 0.74,
p
< 0.01). Distal site measurements of density at the radius as assessed by DXA and HR-pQCT were also associated (
r
= 0.74,
p
< 0.01). Correlations between distal and central site measurements of the hip and of the tibia and radius showed weak to moderate correlation between vBMD by HR-pQCT and QCT (
r
= −0.27 to 0.54). TBS correlated with QCT at the lumbar spine (
r
= 0.35) and to trabecular indices of HR-pQCT at the radius and tibia (
r
= −0.16 to 0.31,
p
< 0.01). There was moderate to strong agreement between measuring techniques when assessing the same skeletal site. However, when assessing correlations between central and distal sites, the associations were only weak to moderate. Our data suggest that the various techniques measure different characteristics of the bone, and may therefore be used in addition to rather than as a replacment for imaging in clinical practice.
Purpose: To assess fracture risk associated with different antiepileptic drugs (AEDs). An increased fracture risk has been reported in patients with epilepsy. Classical AEDs have been associated with ...decreased bone mineral density. The effects of newer AEDs are unknown.
Methods: We undertook a population‐based pharmacoepidemiologic case–control study with any fracture as outcome and use of AEDs as exposure variables (124,655 fracture cases and 373,962 controls).
Results: All AEDs were associated with an increased fracture risk in an unadjusted analysis. After adjustment for prior fracture, use (ever) of corticosteroids, comorbidity, social variables, and diagnosis of epilepsy, carbamazepine CBZ; odds ratio (OR), 1.18; 95% confidence interval (CI), 1.10–1.26, and oxcarbazepine (OXC; 1.14, 1.03–1.26), clonazepam (CZP; 1.27, 1.15–1.41), phenobarbital (PB; 1.79, 1.64–1.95), and valproate (VPA; 1.15, 1.05–1.26) were statistically significantly associated with risk of any fracture. Ethosuximide (0.75, 0.37–1.52), lamotrigine (1.04, 0.91–1.19), phenytoin (1.20, 1.00–1.43), primidone (1.18, 0.95–1.48), tiagabine (0.75, 0.40–1.41), topiramate (1.39, 0.99–1.96), and vigabatrin (0.93, 0.70–1.22) were not statistically significantly associated with fracture risk after adjustment for confounders. The relative increase was modest and in the same range for the significant and nonsignificant results. CBZ, PB, OXC, and VPA displayed a dose–response relation. Fracture risk was more increased by liver‐inducing AEDs (OR, 1.38; 95% CI, 1.31–1.45) than by noninducing AEDs (1.19; 95% CI, 1.11–1.27).
Conclusions: A very limited increased fracture risk is present in users of CBZ, CZP, OXC, PB, and VPA. A limited significant increase cannot be excluded for the other AEDs because of the statistical power.
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