Correlations between Vitamin D Status and Biochemical/Clinical and Pathological Parameters in Primary Hyperparathyroidism

Background To determine the prevalence of vitamin D deficiency and the effects of vitamin D status on parathyroid adenoma weight, clinical and biochemical indices in patients with primary hyperparathyroidism (pHPT) were studied. Methods Eighty patients with pHPT who underwent surgical treatment and in whom the presence of parathyroid adenoma were confirmed histopathologically were studied retrospectively from recorded data files. Patients were divided into three groups: patients with 25-hydroxyvitamin D (25-OHD) concentrations < 15 ng/ml (group 1, n = 44), patients with 25-OHD concentrations > 15–25 ng/ml (group 2, n = 9), and patients with 25-OHD concentrations > 26 ng/ml (group 3, n = 27). Serum calcium, phosphate, alkaline phosphatase, creatinine, and albumin levels and urinary calcium excretion were determined by auto-analyzer. Plasma 25-OHD and parathyroid hormone (PTH) levels were determined by immunoradiometric assay using commercially available kits. Results No statistically significant differences were observed with respect to serum calcium, phosphorus, albumin, and creatinine concentrations between these groups. Serum PTH, alkaline phosphatase concentrations, urinary calcium excretion, parathyroid adenoma weight, and postoperative sixth month PTH concentrations were significantly higher in group 1 patients than in group 2 and group 3 patients. Significant correlations were observed between parathyroid adenoma weight and serum 25-OHD concentrations (r = −0.348, P = 0.020); parathyroid adenoma weight and urinary calcium excretion (r = 0.348, P = 0.021). Multiple regression analysis revealed that parathyroid adenoma weight, serum 25-OHD, and preoperative PTH concentrations correlated independently and significantly with postoperative sixth month PTH concentrations. Conclusions Vitamin D deficiency leads to more severe bone disease, increased parathyroid tumor growth, and delayed postoperative recovery of parathyroid function in patients with primary hyperparathyroidism.     

Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery

BACKGROUND: Abnormalities in calcium and vitamin D metabolism have been reported after bariatric surgery. The purpose of this study was to evaluate vitamin D nutritional status among morbidly obese patients before gastric bypass surgery. METHODS: We prospectively studied 279 morbidly obese patients seeking gastric bypass surgery for vitamin D nutritional status as assessed by serum 25-hydroxyvitamin D level. In addition, serum samples were analyzed for calcium, alkaline phosphatase (AP), intact parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D. RESULTS: Mean patient age was 43 +/- 9 years; 87% of the study patients were women, and 72% were white. Serum calcium and AP levels were normal in 88% and 89% of the patients, respectively. Vitamin D depletion, defined as serum 25-hydroxyvitamin D level 相似文献   

Normocalcemia with elevated parathyroid hormone levels after surgical treatment of primary hyperparathyroidism

BACKGROUND: Thirty percent of patients who undergo successful parathyroidectomy for primary hyperparathyroidism show unexplained elevated postoperative serum parathyroid hormone (PTH) levels despite normocalcemia. METHODS: PTH levels were measured monthly in 97 patients for 6 months after parathyroidectomy. Renal function, 25-OH-vitamin D levels, serum alkaline phosphatase levels, osteocalcin, and bone densitometry were evaluated before and 6 months after surgery. PTH reactivity to calcium loading was tested at the sixth month. RESULTS: Thirty patients had elevated PTH levels despite normocalcemia after parathyroidectomy. Before surgery, these 30 patients had higher PTH and creatinine levels, lower vitamin D levels, and more extensive bone involvement than those with normal postoperative PTH levels. In patients with normal renal function and normal vitamin D levels, postoperative PTH values correlated with preoperative PTH levels but not with bone disease. CONCLUSION: In most cases, elevated PTH levels after surgery is an adaptive reaction to renal dysfunction or vitamin D deficiency. If no adaptive cause can be found, persistent hyperparathyroidism must be suspected.     

Role of Parathyroid Hormone in Bone Fragility of Postmenopausal Women with Vitamin D Insufficiency

Vitamin D insufficiency is related to an increase in PTH, which might be critical for an increase in bone fragility. However, the role of endogenous PTH in vitamin D insufficiency-induced fracture risk remains unclear. The present study was performed to examine the relationships among vitamin D insufficiency, bone fragility, and PTH in 202 Japanese postmenopausal women. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured. The percentages of subjects with 25(OH)D levels below 10, 15, and 20 ng/ml were 5.0, 41.0, and 80.7%, respectively. Serum 25(OH)D levels were negatively related to age and serum levels of Cr and PTH; they were positively related to bone mineral density (BMD). In multiple regression analysis, BMD was significantly related to 25(OH)D levels when adjusted for age, body mass index (BMI), and serum levels of Cr and PTH. Multiple logistic regression analysis showed that lower 25(OH)D levels were significantly related to prevalent fracture risk when adjusted for age, BMI, serum levels of Cr and PTH, as well as femoral neck BMD. The proportion of subjects with prevalent fractures was significantly higher in the group with lower PTH and lower 25(OH)D than in the group with lower PTH and higher 25(OH)D or higher PTH and higher 25(OH)D. In conclusion, vitamin D insufficiency was found to be related to prevalent fracture risk independently of PTH. Functional hypoparathyroidism, rather than functional hyperparathyroidism, might be a risk factor for bone fragility in vitamin D insufficiency.     

Role of parathyroid hormone and therapy with active vitamin D sterols in renal osteodystrophy

Renal osteodystrophy (ROD) represents a spectrum of bone lesions ranging from a high-turnover to a low-turnover state. The expression of the histologic bone lesions is modulated by parathyroid hormone (PTH), vitamin D, calcium, phosphorus, and aluminum that act as major regulators of osteoblastic activity and bone formation rate. The availability of immunometric PTH assays has allowed reasonable prediction of the subtypes of bone lesions in patients with chronic kidney disease (CKD). PTH levels as measured by these assays, however, may not reflect the true bone turnover state during treatment with intermittent active vitamin D. Early diagnosis and appropriate treatment of renal bone disease are essential in preventing the debilitating consequences of ROD on the growing skeleton. Calcitriol and calcium-containing phosphate binders have been the mainstay of treatment for secondary hyperparathyroidism. Complications such as hypercalcemia, vascular calcifications, and the development of adynamic bone may arise from aggressive treatment. New vitamin D analogs and calcium-free phosphate binders are promising in terms of limiting these complications. The management of ROD should be tailored to maintain normal rates of bone formation and turnover with age-appropriate serum calcium and phosphorus levels and with serum PTH levels that correspond to normal rates of skeletal remodeling. These treatment goals would maintain bone health, maximize growth potential, and prevent the development of soft tissue and vascular calcifications.     

Bone health and vascular calcification relationships in chronic kidney disease

Abnormal bone in chronic kidney disease (CKD) may adversely affect vascular calcification via disordered calcium and phosphate metabolism. In this context, bone health should be viewed as a prerequisite for the successful prevention/treatment of vascular calcification (VC) along with controlled parathyroid hormone (PTH) secretion, the use of calcium-based phosphate binders and vitamin D therapy. In CKD patients, VC occurs more frequently and progresses more rapidly than in the general population, and is associated with increased cardiovascular disease (CVD) morbidity and mortality. A number of therapies aimed at reducing PTH concentration are associated with an increase of calcaemia and Ca × P product, e.g. calcium-containing phosphate binders or active vitamin D. The introduction of calcium-free phosphate binders has reduced calcium load, attenuating VC and improving trabecular bone content. In addition, a major breakthrough has been achieved through the use of calcimimetics, as first agents which lower PTH without increasing the concentrations of serum calcium and phosphate. Nowadays, it is becoming evident that even early stage CKD is recognised as an independent CVD risk factor. Moreover, the excess of CVD among dialysis patients cannot be explained entirely on the basis of abnormal mineral and bone metabolism. Hence, much controversy has surrounded the cost-effectiveness of treatment with the new phosphate-binding drugs as well as new vitamin D analogs and calcimimetics. Thus, it seems prudent and reasonable that maintaining bone health and mineral homeostasis should rely on some modifications of standard phosphate binding and calcitriol therapy. Hypophosphataemia and hypercalcaemia in adynamic bone disease (ABD) might be treated by reducing the number of calcium carbonate/acetate tablets in order to increase serum phosphate and decrease serum calcium, which, in turn, might positively stimulate PTH secretion. The same rationale is assumed for the use of a low calcium dialysate. On the other hand, secondary hyperparathyroidism with hyperphosphataemia and hypocalcaemia should be treated with a substantial number of calcium carbonate/acetate tablets in combination with calcitriol and low calcium dialysate in order to decrease serum phosphate and maintain the Ca × P product within K/DOQI guidelines (<4.4 mmol l⁻¹). Finally, it becomes apparent that prevention, with judicious use of calcium-based binders, vitamin D and a low calcium dialysate without adverse effects on Ca × P or oversuppression of PTH, provides the best management of VC and mineral and bone disorder in CKD patients.     

Calcium Malabsorption Does Not Cause Secondary Hyperparathyroidism

We challenge the widespread assumption that malabsorption of calcium per se causes secondary hyperparathyroidism. Serum parathyroid hormone (PTH) does not rise at the menopause despite the fall in calcium absorption, nor is it raised in osteoporotic women with vertebral fractures despite their low calcium absorption. The age-related rise in serum PTH can be accounted for by the age-related fall in serum 25(OH)D and/or decline in renal function with consequent loss of the calcemic action of vitamin D on bone. The reference interval for serum PTH is established in the fasting state when it is at the top of its diurnal cycle and is maintaining serum ionized calcium at the expense of bone to meet the calcium being lost through skin, bowel, and kidneys. There is no evidence that the fasting PTH is influenced by the previous day’s intake or absorption of calcium, although it can be lowered by a large evening calcium supplement. Malabsorption of calcium—like dietary calcium deficiency—is a risk factor for osteoporosis because it reduces or prevents the normal food-related daytime fall in PTH and bone resorption, not because it causes secondary hyperparathyroidism.     

Osteomalacia as a very late manifestation of primary hyperparathyroidism

An 86-year-old woman with a history of treated hyperthyroidism and a 20-year history of untreated primary hyperparathyroidism developed generalized bone pain and a pseudofracture of the midshaft of the left femur. Laboratory examinations revealed elevated serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels. Serum inorganic phosphate was below normal and 25-hydroxyvitamin D levels were low-normal. An undecalcified transiliac bone biopsy specimen following tetracycline double labeling revealed osteomalacia and osteitis fibrosa. Following treatment with vitamin D and phosphate, the serum inorganic phosphate level rose to normal. There was a decrease in bone pain, and the pseudofracture healed. However, the serum calcium, alkaline phosphatase, and C-terminal parathyroid hormone levels remained elevated. Longstanding primary hyperparathyroidism causes chronic hypophosphatemia and may lead to osteomalacia. Osteomalacia and its consequences may be part of the spectrum of bone disease seen in patients with longstanding primary hyperparathyroidism.     

Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity

BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.     

Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

Renal function and 25-hydroxyvitamin D concentrations predict parathyroid hormone levels in renal transplant patients.

BACKGROUND: Recent guidelines suggest supplementation with ergocalciferol (vitamin D(2)) in chronic kidney disease stages 3 and 4 patients with elevated parathyroid hormone (PTH) levels and 25-hydroxyvitamin D (25OHD) levels <75 nmol/l. These guidelines are also applied to renal transplant patients. However, the prevalence rates of 25OHD deficiency and its association with PTH levels in renal transplant populations have not been extensively examined. We aimed to document the prevalence rates of 25OHD deficiency [defined by serum levels <40 nmol/l (<16 ng/ml)] and insufficiency [<75 nmol/l (<30 ng/ml)] in a single renal transplant centre, and examine its relationship with PTH levels. METHODS: Serum 25OHD and PTH concentrations were measured in 419 transplant patients attending a single renal transplant clinic over a 4-month period. Demographic and biochemical data were also collected, including serum creatinine, calcium, phosphate and albumin. Simple and multiple linear regression analysis were performed. RESULTS: In 27.3% of the patients, 25OHD deficiency was present, and 75.5% had insufficiency. On univariate analysis, 25OHD, serum albumin and estimated glomerular filtration rate (eGFR) were significantly associated with PTH levels (P < 0.0001, P = 0.004 and P < 0.0001, respectively). Multiple linear regression demonstrated that only 25OHD, eGFR and serum phosphate were significantly predictive of PTH levels (R(2) = 0.19, P < 0.0001). In this model, a 75 nmol/l increase in 25OHD will only result in a maximal reduction in PTH of 2.0 pmol/l. CONCLUSIONS: We conclude that 25OHD deficiency and insufficiency are common in renal transplant patients and may exacerbate secondary hyperparathyroidism. However, 25OHD, eGFR and phosphate only account for 19% of the variability in PTH levels. In addition, even a large increase in serum 25OHD levels is likely to result in only a small reduction in PTH. Therefore, alternative approaches to managing hyperparathyroidism in renal transplant recipients rather than supplementation with ergocalciferol are warranted.     

Evaluation of markers for calcium homeostasis in a population of obese adults undergoing gastric bypass operations

BACKGROUND: Gastric bypass operation has become a very common procedure for treatment of obesity. Changes in calcium absorption can result in changes in total body calcium, parathyroid hormone (PTH), and vitamin D levels. There is little known about the longterm effects of Roux-en-Y gastric bypass on calcium metabolism and bone homeostasis. STUDY DESIGN: Between January 2000 and January 2006, 535 morbidly obese patients underwent standard Roux-en-Y gastric bypass. All patients were given a standard multivitamin, vitamin D, and calcium supplement starting on day 12 after the operation. Metabolic parameters, such as serum calcium levels, vitamin D, and PTH, both pre- and postoperatively, were measured and compared at several intervals. RESULTS: Four-hundred and forty-four patients were followed for a minimum of 2 years. No statistical significance was found between the pre- and postoperative serum levels of calcium and vitamin D, although vitamin D levels generally increased during the first year after operation. Serum levels of PTH were substantially higher at 18 and 44 weeks after the operation. CONCLUSIONS: Hypocalcemia did not develop in any patients during the postoperative period. Increased PTH levels were observed after gastric bypass operation. This can result in calcium mobilization of calcium from the skeleton and increased renal calcium reabsorption. Total body calcium depletion could occur from bone mobilization, if longterm calcium supplementation is not maintained. Vitamin D supplementation can assist in prevention of bone calcium depletion.     

Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl.

BACKGROUND: Patients with secondary hyperparathyroidism often require therapy that provides long-term control of parathyroid hormone concentrations without increasing calcium and phosphorus concentrations. Cinacalcet modulates the calcium-sensing receptor on the parathyroid gland to reduce secretion of parathyroid hormone and lower serum calcium, phosphorus and calcium-phosphorus product in haemodialysis patients. METHODS: Dialysis patients with secondary hyperparathyroidism [parathyroid hormone (PTH) level > or =300 pg/ml] who were enrolled in one of four phase 2 placebo-controlled studies were eligible to enroll in an open-label extension study in which all patients received cinacalcet. For this extension study, cinacalcet was initiated at 30 mg in all patients and the dose was escalated to a maximum of 180 mg once daily if PTH concentrations were >250 pg/ml. Use of concomitant vitamin D sterols and phosphate binders was not restricted. RESULTS: The analysis of all patients (n = 59) completing 100 weeks of cinacalcet treatment showed long-term control of PTH and calcium-phosphorus product. Approximately 55% achieved a PTH concentration < or =300 pg/ml at the week-100 study visit, and approximately 60% had at least a 30% reduction in PTH from baseline. Serum calcium, phosphorus and the calcium-phosphorus product did not increase during the study. Concomitant vitamin D sterol and phosphate binder therapy remained stable. Cinacalcet was safe and generally well tolerated at doses up to 180 mg/day. CONCLUSIONS: In this long-term study, cinacalcet effectively sustained reductions in PTH for up to 3 years without increasing concentrations of serum calcium, phosphorus or calcium-phosphorus product.     

Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial.

BACKGROUND: To identify differences between the effects of calcitriol and the calcitriol analogue, maxacalcitol, on parathyroid hormone (PTH) and bone metabolisms, we conducted a randomized prospective multicentre study on patients on chronic haemodialysis. METHODS: We randomly assigned 91 patients with secondary hyperparathyroidism [intact PTH (iPTH) > or =150 pg/ml] to have either calcitriol (47 patients) or maxacalcitol (44 patients) therapy, for 12 months after a 1 month control period. Serum electrolytes, bone alkaline phosphatase (bAP), iPTH, total PTH and PTH(1-84) (whole PTH) levels were measured periodically. The first end point was a serum iPTH of <150 pg/ml, the second was the iPTH levels obtained. RESULTS: Treatment was discontinued for various reasons in nine patients in each group, but no serious side effects were observed in either group. The numbers of cases reaching the first end point were not significantly different between the two groups. Serum calcium concentration was significantly higher in the maxacalcitol than the calcitriol group during early treatment, but not at the end of treatment. Throughout the treatment period there were no significant differences between the two groups in serum iPTH, inorganic phosphate, the product of the serum calcium and inorganic phosphorus concentrations, bAP, or the ratio of whole PTH to total PTH minus whole PTH. Nor were the changes in these parameters significantly different between the two groups comparing the patients with moderate to severe hyperparathyroidism (basal iPTH > or =500 pg/ml). CONCLUSION: Calcitriol and maxacalcitol are equally effective on PTH and bone metabolism.     

Primary hyperparathyroidism associated with hypocalcemia in a patient presenting with kidney disease

Elevated serum parathyroid hormone (PTH) level together with hypocalcemia in chronic kidney disease usually suggests secondary hyperparathyroidism. However, primary hyperparathyroidism should also be considered, especially if concomitant vitamin D deficiency is suspected. We report a case of parathyroid adenoma associated with hypocalcemia and metabolic bone disease in a patient presenting with kidney disorder. The patient was successfully treated by parathyroidectomy that was preceded and followed by intensive calcium and vitamin D supplementation.     

Phosphocalcic metabolism: regulation and explorations

Calcium and phosphate play a key role in bone mineralization but have also many other physiological functions. The control of serum phosphate concentration is mandatory to avoid the occurrence of severe metabolic disorders, but is less tightly regulated than serum ionized calcium concentration, which is maintained in a very limited range thanks to parathyroid hormone (PTH) and the active vitamin D metabolite calcitriol. Any change in serum ionized calcium concentration is detected by the calcium sensing receptor (CaSR), a membranous protein located principally in the parathyroid glands and the kidney. A decrease in ionized calcium level inactivates the CaSR, thus stimulating PTH secretion. PTH in turn stimulates the release of calcium and phosphate from bone, renal calcium reabsorption and calcium and phosphate intestinal absorption by inducing renal calcitriol production. Moreover, PTH inhibits phosphate reabsorption in proximal tubular cells, thus contributing towards phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is a circulating factor that decreases serum levels of inorganic phosphate by inhibiting renal phosphate reabsorption and calcitriol production and may have a great physiological role in phosphate homeostasis. Recently, vitamin D actions independent of calcium and phosphate homeostasis were discovered. Basal exploration of phosphocalcic metabolism abnormalities consists in measurement of serum calcium (ionized calcium if possible), phosphate, 25-hydroxy vitamine D and PTH and of 24 hours urinary calcium excretion as well as renal function. Hence, the understanding of physiopathological mechanisms has been improved by newly identified genetic disorders responsible for phophocalcic homeostasis disturbances.     

Hypovitaminosis D osteopathy: is it mediated through PTH, lean mass, or is it a direct effect?

Hypovitaminosis D is increasing worldwide and is associated with low bone mass. The effects of hypovitaminosis D on bone might be direct or mediated through decreased muscle mass and function and/or secondary hyperparathyroidism. This study systematically investigated the relative contribution of lean mass, PTH, and the direct effect of vitamin D as predictors of vitamin D mediated osteopathy in elderly individuals. 460 ambulatory subjects aged 65-85 years had their bone mass and lean body mass measured by a dual-energy X-ray absorptiometry. Serum calcium, phosphorus and alkaline phosphatase, intact parathyroid hormone (PTH) and 25-hydroxyvitamin D (25 OHD) were also measured. Serum 25 OHD correlated with lean body mass in men, r = 0.24, P = 0.002, but not in women; and with bone mass at all skeletal sites in men, r = 0.20-0.30, P < 0.02. Correlations were also noted at all skeletal sites in women except for the spine, r = 0.13-0.18, P < 0.04. In both genders, BMD at sites enriched in cortical bone was 0.4-0.7 SD lower in the group with the lowest vitamin D tertile than that in the group in the highest tertile. After controlling for PTH, the magnitude of the correlations between BMD and 25 OHD remained significant in both genders. After controlling for lean body mass, the magnitude of these correlations did not change in women and decreased but remained significant in men. After adjustment for age and height, both lean body mass and PTH had significant independent contributions to BMD variance at all skeletal sites. After adjustment for age, height, lean mass, and PTH, 25 OHD did not have any significant residual contribution to BMD variance except at the trochanter in men. This study demonstrates that vitamin D osteopathy in the elderly is in large part mediated through lean mass in men and through PTH levels in both genders, with a greater contribution of PTH in women than in men. There was little demonstrable independent relation between serum 25 OHD and bone mass.