Effects of cyclical therapy for osteoporosis using an oral regimen of inorganic phosphate and sodium etidronate: a clinical and bone histomorphometric study

Cyclical therapy for osteoporosis has been proposed as a means to induce a coherently structured improvement in bone remodelling dynamics. This pilot study involved 37 osteoporotic patients with symptomatic vertebral compression fractures, treated with an oral protocol designed to activate endogenous bone turnover and selectively depress osteoclastic bone resorption, utilizing inorganic phosphate and sodium etidronate respectively in sequential 3 monthly cycles. Biochemical parameters were recorded during the first cycle, and quantitative bone histomorphometry was obtained from iliac crest biopsies before and after 23.4 ± 8.5 (SEM) months of treatment. In addition, fracture rates (expressed as new vertebral fractures/1000 patient years) were studied by sequential lateral spinal radiographs. Lumbar bone mineral density (BMD) was assessed by sequential dual-beam photon densitometry. The results demonstrated equivocal biochemical evidence of 2 ° hyperparathyroidism during the initial cycle of therapy with inorganic phosphate. However, fracture rates declined significantly from 640/1000 patient years during the first 15 months therapy to 242/1000 patient years during a further 20 months follow-up (P < 0.01). Lumbar BMD increased over baseline by 8.38 ± 2.87% after 12 months treatmen (P < 0.01). Bone histomorphometric analysis disclosed a modest increment in bone volume from 16.0 to 17.4% tissue volume, and a significant increase in eroded surface from 4.2 ± 0.6 to 6.0 ± 0.9% cancellous surface (P < 0.05). However, histomorphometric parameters of bone formation deteriorated. It is concluded that this cyclical protocol resulted in short-term improvement in trabecular bone mass, but there is no evidence at a cellular level that long-term improvements in bone remodelling occurred.     

Homologous transplantation with fresh frozen bone for dental implant placement can induce HLA sensitization: a preliminary study

It has been related in orthopedic surgeries the HLA sensitization. Thus, we evaluate if the use of fresh-frozen homologous bone (FFHB) for dental implant placement induce anti-HLA sensitization. Six patients were treated with FFHB corticocancellous block grafts. After 6 months, bone biopsies were harvested during implant placement to allow histomorphometric analysis. Vital mineralized tissue (VMT), non-vital mineralized tissue (NVMT) and non-mineralized tissue (NMT) were quantified histomorphometrically. Peripheral blood was collected from the patients before FFHB placement and 6 months after the surgery for anti-HLA analysis. The histomorphometric analysis showed the presence of VMT, NVMT and NMT in 45.56 ± 15.72 %, 14.16 ± 13.39 % and 40.29 ± 12.60 %, respectively. The baseline and 6 months postoperative CTs revealed bone thickness in the order of 5.66 ± 0.67 mm and 8.71 ± 1.52 mm (3.05 ± 1.39 mm). The anti-HLA analysis revealed that two of the six patients (33.3 %) became sensitized, however this was not associated with any FFHB incorporation loss (p > 0.05). A total of 24 implants were placed all of which were osseointegrated after 6 months. Although FFHB-related HLA sensitization does not appear to affect bone incorporation when treating insufficient bone thickness for implant placement, further follow-up is required to determine whether there is an association between HLA sensitization and long-term graft survival.     

Maximum bite force after the replacement of complete dentures

Objective: The aim of the present study was to investigate whether the maximum bite force ( MBF ) can be improved by the replacement of complete dentures for elderly people. Design: Nine edentulous volunteers, mean age 74.2 (± 5.5) years and average denture experience 19.4 ± 19.5 years (1 to 50 years) had replacement dentures made. After a rehearsal session, MBF was recorded with the old dentures, and with the new dentures immediately at insertion, at 3, 8 days, 2–3 weeks, 1, 2, 3 and 6–10 months post insertion ( p‐i. ). MBF was recorded with the central bearing point method using a full‐bridge strain gauge load cell. Data were analysed off‐line using the mean of two peak readings per patient per session. Results: The results indicate that MBF tended to be impaired when replacement dentures were first fitted (n.s.). However, this trend reversed during the first month p‐i. for patients with a “moderate” lower ridge resorption of Atwood grade 3 or 4 (n = 5). Patients with more severe lower ridge resorption Atwood grade 5 or 6 (n = 4) showed a significantly lower MBF over the entire observation period (p0.05) and took longer to regain bite strength. Only patients with moderate bone resorption exceeded their pre‐insertion level of MBF within the observation period of 6–10 months p‐i. Conclusion: The present pilot study suggests that, at least for elderly patients with severe bone resorption, delayed improvement of MBF should be expected with replacement complete dentures.     

Estrogen and progestin effects on urinary calcium and calciotropic hormones in surgically-induced postmenopausal women

Seventeen surgically-induced postmenopausal (PM) women were randomized to receive either 0.625 mg of conjugated estrogens (CE) daily or 150 mg of intramuscular depomedroxyprogesterone acetate (DMPA) every 3 months. Urinary calcium/creatinine ratios were significantly higher than ratios of premenopausal controls before treatment, but were lower in all patients 2 months after both types of treatment. Compared to controls, all PM patients had similar levels of serum PTH and 25 hydroxy vitamin D before and after treatment. As a group, PM patients had lower levels of 1.25-dihydroxyvitamin D. In 5 patients who had levels which were below the normal range, 3 were treated with CE and 2 received DMPA. These patients all had significant increases in 1,25-dihydroxyvitamin D after treatment. Serum calcitonin did not change with either CE or DMPA treatment. These data suggest that, while both CE and DMPA lower calcium excretion in PM women, the mechanism(s) for the effects of hormonal treatment on bone resorption remain unsettled.     

Glucocorticoid-induced osteoporosis

Osteoporosis is a common and serious complication of glucocorticoid therapy, resulting in increased risk of fragility fractures. Recent studies indicate that fracture risk is increased even at low doses of glucocorticoids and that this increased risk is seen soon after the commencement of glucocorticoid therapy. Both increased bone resorption and reduced bone formation contribute to bone loss, which affects cortical and cancellous sites. A number of interventions have been shown to prevent glucocorticoid-induced bone loss, although the strongest evidence exists for the bisphosphonates etidronate, alendronate and risedronate. Primary prevention of bone loss should be considered in all high-risk individuals taking oral glucocorticoids for 3 months or more, for example those aged 65 years or over or those with a previous fragility fracture. In other glucocorticoid-treated individuals, the decision to treat should be based on bone densitometry.     

Bone Disease in Newly Diagnosed Lupus Nephritis Patients

Introduction

Bone loss in Lupus Nephritis (LN) patients is common and multifactorial. The aim of this study was to evaluate the bone status of newly diagnosed LN patients and their correlation with inflammatory factors involved in LN physiopathology.

Methods

We studied 15 pre-menopausal patients with ≤2 months of diagnosed SLE and LN. Patients with prior kidney or bone disease were excluded. In addition to biochemical evaluation (including 25-hydroxyvitamin D₃ [25(OH)D] and Monocyte Chemotactic Protein (MCP1) dosage), we performed bone biopsies followed by osteoblast culture, histomorphometric and immunohistochemistry analysis.

Results

LN patients presented a mean age of 29.5±10 years, a proteinuria of 4.7±2.9 g/day and an estimated glomerular filtration rate (GFR) of 37(31–87) ml/min/1,73 m². They were on glucocorticoid therapy for 34±12 days. All patients presented vitamin D insufficiency (9.9±4.4 ng/ml, range 4–20). Urinary MCP1 correlated negatively with 25(OH)D (r = −0.53, p = 0.003) and positively with serum deoxypyridinoline (r = 0.53, p = 0.004). Osteoblasts isolated from LN bone biopsies presented a significantly higher expression of MCP-1 when compared to controls (32.0.±9.1 vs. 22.9±5.3 mean fluorescence intensities, p = 0.01). LN patients presented a significantly reduced osteoid volume, osteoid thickness, osteoid surface, mineralization surface and bone formation rate, associated with an increased eroded surface and osteoclast surface. Patient’s bone specimens demonstrated a reduced immunostaining for osteoprotegerin (0.61±0.82 vs. 1.08±0.50%, p = 0.003), and an increased expression of Receptor Activator of NF-κB ligand (RANKL) (1.76±0.92 vs. 0.41±0.28%, p<0.001) when compared to controls.

Discussion

Newly diagnosed LN patients presented a significant disturbance in bone metabolism, characterized by an impaired bone formation and mineralization, associated with an increase in resorption parameters. Glucocorticoid use, vitamin D insufficiency and inflammation might be involved in the physiopathology of bone metabolism disturbance.     

Increased PTH and 1.25(OH)(2)D levels associated with increased markers of bone turnover following bariatric surgery

The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)(2)D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers.     

Cyclic hydrostatic pressure and particles increase synthesis of 1,25-dihydroxyvitamin D3 by human macrophages in vitro

1,25-Dihydroxyvitamin D(3) has a pivotal role in bone resorption and osteoclast activity. As activated macrophages are known to synthesise 1,25-dihydroxyvitamin D(3), this study examined whether pressure modulated its synthesis. Pressure and particles have been shown to increase synthesis of pro-resorptive cytokines and other factors by cultured macrophages. Human peripheral blood macrophages were isolated, cultured and exposed to pressure (similar to that found in the human joint) and/or particles. Synthesis of 1,25-dihydroxyvitamin D(3) by macrophages was assayed using high pressure liquid chromatography and in situ hybridization. Synthesis of 1,25-dihydroxyvitamin D(3) but not 24,25-dihydroxyvitamin D(3) was increased in macrophages under pressure. In situ hybridization demonstrated an increase in 1alpha-hydroxylase expression in response to pressure or particles and simultaneous exposure to both stimuli generated higher expression of 1alpha-hydroxylase. In conclusion, this is the first study to demonstrate that mechanical loading, in the form of pressure, stimulates 1,25-dihydroxyvitamin D(3) synthesis in human macrophages. These findings have implications for the in vivo situation, as they suggest that 1,25-dihydroxyvitamin D(3) could be one factor stimulating osteoclastic bone resorption in pathologies, such as arthritis or implant loosening, where intra-articular or intra-osseous pressure is raised or where wear particles interact with macrophages.     

Differential effects of Vitamin D analogs on bone formation and resorption

Deficiency in Vitamin D and its metabolites leads to a failure in bone formation primarily caused by dysfunctional mineralization, suggesting that Vitamin D analogs might stimulate osteoblastic bone formation and mineralization. In this study, we compare the effect of selected Vitamin D analogs and active metabolite, 1alpha,25-dihydroxyvitamin D(3), 19-nor-1alpha, 25-dihydroxyvitamin D(2), and 1alpha-hydroxyvitamin D(2) or 1alpha,25-dihydroxyvitamin D(2) on bone formation and resorption. In a mouse calvariae bone primary organ culture system, all Vitamin D analogs and metabolite tested-stimulated collagen synthesis in a dose-dependent manner and 19-nor-1alpha, 25-dihydroxyvitamin D(2) was the most efficacious among three. 19-nor-1alpha, 25-dihydroxyvitamin D(2) and 1alpha,25-dihydroxyvitamin D(2) showed similar potencies and 1alpha,25-dihydroxyvitamin D(3) was less potent than others. Osteocalcin was also up-regulated in a dose-dependent manner, suggesting that the three Vitamin D analogs have the equal potencies on bone formation. 25-Hydroxyvitamin D-24-hydroxylase expression was induced in a dose-dependent manner and 19-nor-1alpha, 25-dihydroxyvitamin D(2) was less potent than other two compounds. In a mouse calvariae organ culture, all induced a net calcium release from calvariae in a dose-dependent manner, but the potency is in the order of 1alpha,25-dihydroxyvitamin D(2) congruent with1alpha,25-dihydroxyvitamin D(3)>19-nor-1alpha, 25-dihydroxyvitamin D(2). In a Vitamin D/calcium-restricted rat model, all caused an elevation in serum calcium in a dose-dependent manner. There is no significant difference between 1alpha,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(2) in potencies, but 19-nor-1alpha, 25-dihydroxyvitamin D(2) is at least 10-fold less potent than the other two compounds. Our results suggest that Vitamin D analogs have direct effects on bone resorption and formation, and 19-nor-1alpha, 25-dihydroxyvitamin D(2) may be more effective than 1alpha,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(2) on stimulating anabolic bone formation.     

First use of the RANKL antibody denosumab in Osteogenesis Imperfecta Type VI

Osteogenesis imperfecta (OI) is a genetically heterogeneous disease leading to bone fragility. OI-VI is an autosomal-recessive form caused by mutations in SERPINF1. There is experimental evidence suggesting that loss of functional SERPINF1 leads to an activation of osteoclasts via the RANK/RANKL pathway. Patients with OI-VI show a poor response to bisphosphonates. We report on four children with OI-VI who had shown continuously elevated urinary bone resorption markers during a previous treatment with bisphosphonates. We treated these children with the RANKL antibody denosumab to reduce bone resorption. Intervention and results: Denosumab (1 mg/kg body weight) was injected s.c. every 3 months. There were no severe side effects. Markers of bone resorption decreased to the normal range after each injection. N-terminal Propeptide of collagen 1 was measured in the serum during the first treatment cycle and decreased also. Urinary deoxypyridinoline/creatinine was monitored in a total of seven treatment cycles and indicated that bone resorption reached the pre-treatment level after 6-8 weeks. Conclusion: This was the first use of denosumab in children with OI-VI. Denosumab was well tolerated, and laboratory parameters provided evidence that the treatment reversibly reduced bone resorption. Therefore, denosumab may be a new therapeutic option for patients with OI-VI.     

Preventive effects of risedronate and calcitriol on cancellous osteopenia in rats treated with high-dose glucocorticoid.

We compared the effects of risedronate (Ris) and calcitriol (Cal) on cancellous osteopenia in rats treated with high-dose glucocorticoid (GC). Forty female Sprague-Dawley rats, 4 months of age, were randomized by the stratified weight method into four groups of 10 rats each according to the following treatment schedule: intact control, and GC administration with vehicle, Ris, or Cal. The GC (methylprednisolone sodium succinate, 5.0 mg/kg, s.c.), Ris (10 microg/kg, s.c.), and Cal (0.1 microg/kg, p.o.) were administered 3 times a week. At the end of the 4-week treatment period, bone histomorphometric analysis was performed for cancellous bone of the proximal tibial metaphysis. The GC administration decreased cancellous bone volume (BV/total tissue volume [TV]), trabecular number (Tb N), and trabecular thickness (Tb Th), as a result of increased bone resorption and decreased bone formation. Ris treatment markedly increased cancellous BV/TV and Tb N above the control level as a result of suppressed bone turnover. On the other hand, Cal treatment attenuated the GC-induced decrease in cancellous BV/TV and Tb Th as a result of suppressed bone resorption and maintained bone formation. This study showed the differential effects of Ris and Cal on cancellous osteopenia in rats treated with high-dose GC.     

Hispidulin Exerts Anti-osteoporotic Activity in Ovariectomized Mice via Activating AMPK Signaling Pathway

To investigate the effect of Hispidulin on ovariectomy (OVX)-induced bone loss in mice. Female mice subjected to OVX were treated with Hispidulin for 8 weeks. The total body bone mineral density was measured at the beginning and after the OVX at a time interval of 4 weeks. Micro-computed tomography of the tibia, bone histomorphometric analysis of the femur, and biomechanical analysis of tibia, vertebra, and femoral head were performed to fully evaluate the anti-osteoporotic effect of Hispidulin. Western blot analysis was performed to determine the level of activated AMPK. Hispidulin treatment effectively prevented OVX-induced body weight loss and attenuated OVX-induced bone loss. Hispidulin treatment also decreased trabecular spacing in OVX mice. The suppressing effect of Hispidulin on osteoclast surface and number was also found via histomorphometric analysis. Western blot analysis revealed that Hispidulin significantly elevated the activated AMPK levels. Our findings suggest that Hispidulin exerts anti-osteoporotic and bone resorption attenuating effects via activating the AMPK signaling pathway.     

Prognostic significance of the histomorphometric features of bone marrow trephine biopsies in patients with chronic myeloid leukemia

OBJECTIVE: To study the correlation of histomorphometric data of bone marrow trephine biopsies at the time of initial diagnosis in chronic myeloid leukemia (CML) patients with the patient prognosis. STUDY DESIGN: A total of 40 CML patients were divided equally in group I (developed accelerated phase or blast crisis within 18 months of initial diagnosis of chronic phase of CML) and group II (developed accelerated phase or blast crisis > 30 months after initial diagnosis of chronic phase of CML). The clinical, hematologic and histomorphometric data were compared in the 2 groups of CML patients. RESULTS: The percentage of bone marrow promyelocytes was significantly increased in group I. On morphometry, the number of blasts per square millimeter, the area of reticulin fibers per square millimeter and the percentage area occupied by reticulin fibers were statistically significant. CONCLUSION: There seems to be grounds for hope for predicting prognosis of CML patients at initial diagnosis based on histomorphometric findings. The percentage area of reticulin fibers and the number of blasts per square millimeter are important prognostic predictors in histomorphometry data.     

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1‐year follow‐up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6‐month exercise‐based weight loss program and returned for follow‐up at 18 months. Dual‐energy X‐ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m². They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow‐up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (?1.7 ± 3.5%; P = 0.002) and hip (?0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C‐terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (?0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: ?3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone‐deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.     

On an attempt to treat primary and secondary osteoporosis with human growth hormone.

Three male patients with severe osteoporosis were treated with human growth hormone. One of them had a primary osteoporosis, the two others osteogenesis imperfecta. The duration of therapy was 8 to 15 months and average doses per day were 1.45 to 2.3 mg. While clinical and 47calcium kinetic data failed to prove marked influences of the treatment, histomorphometry of bone biopsies showed indisputable changes. There was an increase of periosteal new bone formation as well as of intracortical bone resorption, while at the same time the relative activity of osteoblasts on endosteal surfaces showed a significant increase.     

Treatment of growth failure in juvenile chronic arthritis

We retrospectively assessed linear growth and final height in a group of 24 patients suffering from juvenile idiopathic arthritis (JIA) during childhood, receiving steroid therapy. In these patients, a significant loss of height (-2.7 +/- 1.5 SDS) occurred in the first years of the disease which was positively correlated with prednisone therapy duration. After remission of the disease and prednisone discontinuation, most of the patients (70%) had catch-up growth but 30% had a persistent loss of height. Their mean final height was strongly correlated with their mean height at the end of steroid therapy and was significantly different between the group of patients with catch-up growth (-1.5 +/- 1.6 SDS) and the group without catch-up growth (-3.6 +/- 1.2 SDS). This pattern of growth observed in JIA patients should help us to define strategies of GH treatment in these patients in order to improve their final height. We have previously reported the beneficial effects on growth and body composition of a 1-year GH treatment in a group of 14 growth-retarded patients suffering from juvenile idiopathic arthritis, receiving glucocorticoid therapy. These patients (n = 13) were treated again with GH at the same dosage (0.46 mg/kg/week) for another 3-year period. GH treatment markedly increased growth velocity in these patients, but had a minor effect on SDS height suggesting that these children will remain short at adult age. Using GH earlier in these patients during the course of their disease may prevent growth deterioration and metabolic complications induced by chronic inflammation and long-term steroid therapy.     

Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.     

Abnormalities of Vitamin D and Calcium Metabolism after Surgical Treatment of Morbid Obesity: A Study of 136 Patients

ObjectiveTo assess the effect of bariatric surgical treatment of morbid obesity on bone mineral metabolism.MethodsWe analyzed pertinent vitamin D and calcium metabolic variables in 136 patients who had undergone a malabsorptive bariatric operation. Measurements of bone mineral density (BMD), serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D [1,25-(OH)₂D], parathyroid hormone (PTH), calcium, phosphorus, and alkaline phosphatase were performed. Statistical analyses assessed correlations among various factors.ResultsThe mean age (± SD) of the study group was 48.34 ± 10.28 years. Their mean weight loss was 114.55 ± 45.66 lb, and the mean duration since the bariatric surgical procedure was 54.02 ± 51.88 months. Seventeen patients (12.5%) had a T-score of -2.5 or less, and 54 patients (39.7%) had a T-score between –1.0 and –2.5. Of 119 patients in whom serum 25-OHD was measured, 40 (34%) had severe hypovitaminosis D (25-OHD < 8 ng/mL), and 50 patients (42%) had low hypovitaminosis D (serum 25-OHD 8 to 20 ng/mL). The magnitude of weight loss correlated negatively with serum 25-OHD, calcium, phosphorus, and calcium × phosphorus product values and positively with serum alkaline phosphatase level. Serum 25-OHD and calcium concentrations correlated positively with the BMD. PTH, serum 1,25-(OH)₂D, and alkaline phosphatase concentrations correlated negatively with the BMD, a reflection of the presence of secondary hyperparathyroidism, an accelerated conversion of 25-OHD to 1,25-(OH)₂D by the elevated PTH levels, and increased osteoblastic activity. The mean daily vitamin D supplementation was 6,472 ± 9,736 IU.ConclusionHypovitaminosis D and subsequent bone loss are common in patients who have undergone a bariatric surgical procedure for morbid obesity. These patients require rigorous vitamin D supplementation. (Endocr Pract. 2007;13:131-136)     

Possible case of hyperparathyroidism in a Roman period skeleton from the Dakhleh Oasis, Egypt, diagnosed using bone histomorphometry

A histomorphometric study of thin femoral head sections of a skeletal sample from the Dakhleh Oasis, Egypt, dated from circa 36 B.C. to 400 A.D., identified an adult female (Dk31-A1) in her mid-50s with a high percentage resorption surface with tunneling resorption as is typically found in hyperparathyroidism. Five static histomorphometric bone parameters were measured with the following results for this individual: 1) mean wall thickness, 41.94 micron, 2) trabecular bone volume, 18.54%, 3) surface volume, 4,070 mm2/cm3, 4) mean trabecular diameter, 132 microns, and 5) total resorption surface, 12.31%. The overall histomorphometric features and differential diagnosis support the diagnosis of hyperparathyroidism. We conclude that histomorphometry of dried bone, particularly in this case where preservation is ideal, is a valuable investigative technique for paleopathology.     

The influence of hyperthyroidism and glucocorticosteroid treatment on bone metabolism in patients with Graves' disease and ophthalmopathy

The aim of the study was to assess influence of hyperthyroidism and glucocorticosteroid treatment on changes of bone turnover markers in patients with Graves' disease and thyroid ophthalmopathy (TO). MATERIAL AND METHODS: Three groups of patients were included in the study. Group I was composed of 26 euthyroid Graves' disease patients with TO suitable for steroid treatment. Group II included 14 hyperthyroid Graves' patients without TO treated medically with anti-thyroid drugs. Group III (control group) included 20 healthy volunteers. Levels of the bone formation marker, i.e. bone-specific alkaline phosphatase (BALP) and the bone resorption marker, i.e. deoxypyridinoline (DPD) were measured in the group I before steroid treatment administration, after 3 methylprednisolone i.v. pulses and after completing the oral prednisone treatment. In the group II levels of BALP and DPD were assessed twice: before treatment of hyperthyroidism and after 6 months since euthyroid state had been achieved. In the group III levels of BALP and DPD were measured once in the basal conditions. RESULTS: Mean initial levels of BALP in groups I and II did not differ significantly and were increased when compared to healthy volunteers. In the group I a transient significant decrease in BALP levels after 3 i.v. pulses of methylprednisolone was observed, followed by a significant increase in BALP after completing the oral prednisone therapy. The achievement of euthyroid state in Graves' patients (II) did not influence significantly BALP values. In the group I initial DPD levels were significantly lower than those in group II and higher than those in the control group (III). During steroid treatment of TO (group I) no dynamic changes of DPD levels were observed. The achievement of euthyroid state in group II was accompanied by a significant decrease in DPD levels, which were however than those in the control group. CONCLUSIONS: 1. In hyperthyroid state is associated with the profound stimulation of bone resorption, and to a lesser extent of bone formation. 2. The achievement of euthyroid state causes a rapid inhibition of bone resorption and maintains a compensatory stimulation of bone formation. 3. Glucocorticosteroid treatment with methylprednisolone i.v. pulses and orally administered prednisone do not influence significantly the processes of bone formation and bone resorption.