Effect of Vitamin D Therapy on Bone Turnover Markers in Postmenopausal Women with Osteoporosis and Osteopenia

ObjectiveTo (7) assess the rate of reduction in bone turnover with vitamin D and bisphosphonate therapies and (2) evaluate the clinical utility of bone-specific alkaline phosphatase (BSAP) in monitoring treatment response.MethodsWe retrospectively reviewed medical records of patients with newly diagnosed osteopenia and osteoporosis from 2002 to 2009 at Loyola University Medical Center. A cohort of postmenopausal women with hip or spine T-scores of less than -1, normal serum creatinine, and no prior vitamin D or bisphosphonate therapy was divided into vitamin D-deficient (n = 29) and vitamin D-sufficient (n = 13) groups. Vitamin D-deficient patients received high-dose vitamin D, whereas vitamin D-sufficient patients received orally administered bisphosphonates. BSAP levels at baseline and 1 year were compared.Resultsvitamin D therapy in the group with vitamin D deficiency led to a 26.7% decrease in BSAP (P < .01). Bisphosphonate therapy in the vitamin D-sufficient group led to a 32.7% decrease in BSAP (P = .01). The magnitude of BSAP change in the 2 study groups (6.74 ± 6.48 μg ∕ L and 8.72 ± 9.94 μgZL) did not differ significantly (P = .45).ConclusionThe results of this study suggest that correction of vitamin D deficiency in patients with osteopenia and osteoporosis can lead to a decrease in bone turnover as measured by BSAP and that the magnitude of this reduction is similar to that achieved with orally administered bisphosphonates. (Endocr Pract. 2011;17:873-879)     

Consensus and Controversy Regarding Osteoporosis in the Pediatric Population

ObjectiveTo review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence.MethodsThe medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis.ResultsChildhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass—variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise-associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients.ConclusionBone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood. (Endocr Pract. 2007;13:513-520)     

Vitamin D,Calcium, and Cardiovascular Mortality: A Perspective from A Plenary Lecture Given at the Annual Meeting of the American Association of Clinical Endocrinologists

ObjectiveTo examine data showing associations between serum 25-hydroxyvitamin D levels and calcium intake and cardiovascular mortality.MethodsThe articles reviewed include those published from 1992-2011 derived from search engines (PubMed, Scopus, Medscape) using the following search terms: vitamin D, calcium, cardiovascular events, cardiovascular mortality, all-cause mortality, vascular calcification, chronic kidney disease, renal stones, and hypercalci- uria. Because these articles were not weighted (graded) on the level of evidence, this review reflects my own perspective on the data and how they should be applied to clinical management.ResultsFor skeletal health, vitamin D and calcium are both needed to ensure proper skeletal growth (modeling) and repair (remodeling). Nutritional deficiencies of either vitamin D or calcium may lead to a spectrum of metabolic bone disorders. Excessive consumption of either nutrient has been linked to a variety of medical disorders, such as hypercalcemia or renal stones. There have also been associations between vitamin D or calcium intake and cardiovascular disease. However, neither of these associations have established evidence nor known causality for increasing cardiovascular risk or all-cause mortality in patients with creatinine clearances greater than 60 mL/ min. In patients with more severe chronic kidney disease, stronger data link excess calcium (or phosphorus) intake and increase in vascular calcification, but not mortality. The safe upper limit for vitamin D intake is at least 4000 IU daily and probably 10 000 IU daily; for calcium, the safe upper limit is between 2000 and 3000 mg daily.ConclusionsWhile no solid scientific evidence validates that serum vitamin D levels between 15 and 70 ng/ mL are associated with increased cardiovascular disease risk, stronger but inconsistent evidence shows an association between calcium supplementation greater than 500 mg daily and an increase in cardiovascular disease risk. Most professional societies suggest that replacement levels of these nutrients be personalized with the goal of reaching a 25-hydroxyvitamin D concentration between 30 and 50 ng/ mL and a calcium intake of 1200 mg daily. (Endocr Pract. 2011;17:798-806)     

Prevalence of Osteoporosis in Ambulatory Postmenopausal Women from A Semiurban Region in Southern India: Relationship to Calcium Nutrition and Vitamin D Status

ObjectiveTo assess the prevalence of osteoporosis in healthy ambulatory postmenopausal Indian women as measured by dual-energy x-ray absorptiometry and to study the dietary calcium intake and vitamin D status and their influence on bone mineral density (BMD).MethodsWe conducted a community-based crosssectional study in a semiurban region. A randomized cluster sampling technique was used. The study cohort consisted of 150 ambulatory postmenopausal women (≥ 50 years old). Dual-energy x-ray absorptiometry for BMD was performed at the lumbar spine and femoral neck. Dietary calcium intake and biochemical variables were assessed.ResultsThe prevalence of osteoporosis was 48% at the lumbar spine, 16.7% at the femoral neck, and 50% at any site. The mean dietary calcium intake was much lower than the recommended intake for this age-group. There was a significant positive correlation between body mass index and BMD at the lumbar spine and the femoral neck (r = 0.4; P = .0001). BMD at the femoral neck was significantly less (mean, 0.657 versus 0.694 g/cm²) in the vitamin D-insufficient study subjects in comparison with the vitamin D-sufficient women (P = .03).ConclusionThe high prevalence of osteoporosis and vitamin D insufficiency in this semiurban group of postmenopausal women in India is a major health concern. Measures such as adequate calcium intake and vitamin D supplementation in women of this age-group may be beneficial. (Endocr Pract. 2008;14:665-671)     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

The Effects of Hyponatremia on Bone Density and Fractures: A Systematic Review and Meta-Analysis

Objective: Hyponatremia decreases bone mineral density and is a major risk factor for fragility fractures. Objectives of our systematic review and meta-analysis were to analyze the overall effects of hyponatremia on bone fractures, osteoporosis, and mortality.Methods: We extracted data from Medline, Cochrane Central, and EMBASE 1960–2017 and conference abstracts from 2007–2017. We included studies with data on serum sodium, fractures, bone density, or diagnoses of osteoporosis. Studies were independently reviewed by two authors and assessed for bias using the Newcastle-Ottawa scale. Random effect models meta-analysis was used when at least three studies reported the same outcome measures. We reported summary odds ratios (ORs) and 95% confidence intervals (CIs).Results: We included 26 studies for qualitative analysis. Fifteen studies were included in the meta-analysis to evaluate the effects of hyponatremia on fractures, four studies for bone mineral density changes, and six for mortality. Hyponatremia increased the odds of fractures at all sites (summary OR, 2.34 [95% CI, 1.86, 2.96]. There was an increase in the odds of osteoporosis (summary OR, 2.67 [95% CI, 2.07, 3.43]). Mortality risk among the included studies remained high (summary OR, 1.31 [95% CI, 1.16, 1.47]).Conclusion: Our meta-analysis confirms a statistically significant association of hyponatremia with bone fractures and osteoporosis along with higher mortality. Long-term prospective studies evaluating the impact of correcting hyponatremia on bone health, fractures, and mortality are required.Abbreviations: AVP = arginine vasopressin; CI = confidence interval; CKD = chronic kidney disease; OR = odds ratio; SIADH = syndrome of inappropriate antidiuretic hormone     

Endocrine-Metabolic Pathophysiologic Conditions and Treatment Approaches After Kidney Transplantation

ObjectiveTo review pathophysiologic conditions and diagnostic and therapeutic approaches in the management of endocrine-metabolic disorders after kidney transplanta tion (KT).MethodsWe discuss the assessment of diabetes mel litus (DM), hyperlipidemia, hypertension, and disturbances of bone and mineral metabolism after KT.ResultsKT offers patients with end-stage kidney disease substantial improvement in life expectancy and quality of life. Despite amelioration of renal dysfunction, however, these patients are at risk for the deterioration of existing and the development of new endocrine pathologic conditions. Pretransplant DM and new-onset diabetes after transplantation are associated with worse patient and graft survival. Little is known about preventing new-onset dia betes after transplantation and managing DM shortly after KT. In addition to glycemic control in patients with dia betes, management of cardiovascular risk factors includes appropriate recognition and treatment of hypertension and dyslipidemia. After KT, patients are at considerable risk for derangements in calcium and vitamin D metabolism. Immunosuppressive medications may cause compromised glucose and lipid metabolism, which may, in turn, contrib ute to the progression of preexisting and the development of new posttransplant endocrinopathies.ConclusionClinical care of kidney transplant patients should include a comprehensive endocrine assessment before and after KT in close collaboration with transplant nephrology providers. A referral to an endocrinologist should be initiated early during the pretransplant stage, and collaborative management should be maintained in kidney transplant patients to improve clinical outcomes. (Endocr Pract. 2012;18:579-590)     

慢性肾脏病-矿物质和骨代谢紊乱导致血管钙化的分子机制研究进展

慢性肾脏病-矿物质和骨代谢紊乱(CKD-MBD)所导致的血管钙化是增加CKD患者发生心血管事件的独立危险因素。钙磷平衡的破坏、氧化应激的增加、钙化抑制剂的丢失、RANKL表达的增加等均被认为与CKD患者血管钙化的发生有关。此外,受损的骨质能够进一步扰乱血清钙磷和甲状旁腺激素水平,从而促进CKD患者发生血管钙化。磷结合剂和双膦酸盐类药物是目前治疗CKD-MBD所致的血管钙化是治疗的常用方法,可以改善骨质疏松以及血管钙化。本文就近年来CKD-MBD血管钙化发生机制的研究进展进行了综述。     

Secondary Causes of Osteoporosis

ObjectiveTo provide an updated review of several causes of secondary osteoporosis as well as screening recommendations for these disorders.MethodsWe conducted an updated review of the literature published since 2006 on secondary causes of osteoporosis. This information has been added to the relevant data published between 1990 and 2006, which was included in our prior review from 2006. This current review also includes recent clinical guidelines recommendations.ResultsSecondary osteoporosis occurs in almost two thirds of men, more than half of premenopausal women, and about 30% of postmenopausal women. Its causes are vast, and they include hypogonadism, medications, hyperthyroidism, vitamin D deficiency, primary hyperparathyroidism, solid organ transplantation, gastrointestinal diseases, hematologic diseases, Cushing's syndrome, and idiopathic hypercalciuria. These causes have their own pathogenesis, epidemiologic features, and effects on the skeleton.ConclusionThe causes of secondary osteoporosis are numerous, and an understanding of their characteristics with respect to bone density and potential fracture risk is essential in the management of osteoporosis. A heightened awareness of the possibility of their existence is necessary to provide optimal care. (Endocr Pract. 2013;19:120-128)     

Correlation of Body Mass Index and Age with Osteoporosis Probability in Patients with Primary Hyperparathyroidism

ObjectiveCurrently, there are limited markers to predict the osteoporosis probability in patients with primary hyperparathyroidism. We studied the relationship between various parameters and results of DXAs at various skeletal sites.MethodsRetrospective review of data for 218 patients with primary hyperparathyroidism was performed. Age, BMI, bone mineral density, serum total calcium, ionized calcium, intact parathyroid hormone, albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-hour urinary calcium levels and parathyroid tumor weight were analyzed. Two different statistical models- linear regression and multivariate logistic regression were performed.ResultsAt the lumbar spine, with the linear model, BMI (P < .001), alkaline phosphatase (P < .001), and ionized calcium (P < .001) significantly correlated with T scores; whereas with the logistic model, BMI was the only variable predicting osteoporosis probability.At the femoral neck, BMI (P < .022), 25-hydroxy vitamin D (P < .001), 1,25-dihydroxy vitamin D (P < .034) correlated with T scores; whereas both BMI (P < .029) and age (P < .051) were the significant variables that predicted osteoporosis.At the total hip, BMI (P < .001) and age (P < .001) correlated with T scores; whereas with the logistic model, only BMI (P < .016) predicted osteoporosis. At the forearm, a model could not be generated due to limited number.ConclusionIn patients with primary hyperparathyroidism, BMI strongly correlated with T scores and probability of osteoporosis.     

FGF-23 Is a Negative Regulator of Prenatal and Postnatal Erythropoiesis

Abnormal blood cell production is associated with chronic kidney disease (CKD) and cardiovascular disease (CVD). Bone-derived FGF-23 (fibroblast growth factor-23) regulates phosphate homeostasis and bone mineralization. Genetic deletion of Fgf-23 in mice (Fgf-23^−/−) results in hypervitaminosis D, abnormal mineral metabolism, and reduced lymphatic organ size. Elevated FGF-23 levels are linked to CKD and greater risk of CVD, left ventricular hypertrophy, and mortality in dialysis patients. However, whether FGF-23 is involved in the regulation of erythropoiesis is unknown. Here we report that loss of FGF-23 results in increased hematopoietic stem cell frequency associated with increased erythropoiesis in peripheral blood and bone marrow in young adult mice. In particular, these hematopoietic changes are also detected in fetal livers, suggesting that they are not the result of altered bone marrow niche alone. Most importantly, administration of FGF-23 in wild-type mice results in a rapid decrease in erythropoiesis. Finally, we show that the effect of FGF-23 on erythropoiesis is independent of the high vitamin D levels in these mice. Our studies suggest a novel role for FGF-23 in erythrocyte production and differentiation and suggest that elevated FGF-23 levels contribute to the pathogenesis of anemia in patients with CKD and CVD.     

Severe Hypophosphatemic Osteomalacia Secondary to Fanconi Syndrome Due to Adefovir: A Case Report

ObjectiveGeneralized proximal, type 2, renal tubular acidosis, also known as Fanconi syndrome, is a generalized dysfunction of the proximal renal tubule characterized by impaired reabsorption and increased urinary loss of phosphate and other solutes, such as uric acid, glucose, amino acids, and bicarbonate. Chronic hypophosphatemia is the second most common cause of osteomalacia after vitamin D deficiency in adult patients and can have a heterogeneous presentation, ranging from mild symptoms such as muscle weakness and skeletal pain to more severe presentation, such as disabling myopathy, severe bone and joint pain, difficulty walking, and even bone fractures.MethodsThis report describes a case of severe hypophosphatemic osteomalacia with multiple fragility fractures induced by adefovir, which was worsened and confounded by a previous treatment with zoledronic acid and required prolonged intravenous potassium phosphate administration.ResultsWe highlight the limited diagnostic value of dual X-ray absorptiometry and bone scintigraphy in this challenging diagnosis. Bone metabolism should always be assessed in patients treated with adefovir for early detection of osteomalacia due to Fanconi syndrome.ConclusionAlthough rare, this condition may be life-threatening and mimic other bone metabolic disorders that are treated with drugs that may further impair phosphate balance. (Endocr Pract. 2014;20:e246-e249)     

Increase in Bone Mass After Correction of Vitamin D Insufficiency in Bisphosphonate-Treated Patients

ObjectiveTo assess the relative contribution of vitamin D insufficiency to loss of bone mineral density (BMD) in patients taking bisphosphonates.MethodsPatients were eligible for inclusion if they had osteoporosis or osteopenia and demonstrated a decline in BMD during the preceding year while taking stable doses of alendronate or risedronate, plus supplemental calcium and vitamin D. Patients with previously known secondary causes of osteoporosis were excluded from the study. Eligible patients underwent prospective measurement of bilateral hip and lumbar spine BMD by dual-energy x-ray absorptiometry, serum 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D, intact parathyroid hormone, osteocalcin, and thyroid-stimulating hormone (thyrotropin), and urinary calcium:creatinine ratio.ResultsAnnual BMD was assessed in 175 previously bisphosphonate-responsive patients with low BMD. Of the 175 patients, 136 (78%) had either a significant interval increase or no change in BMD, whereas 39 (22%) had a significant decrease. Of the 39 patients who lost BMD, 20 (51%) had vitamin D insufficiency (25-OHD < 30 ng/mL). After a single course of orally administered vitamin D₂ (500,000 IU during a 5-week period), the 25-OHD level returned to normal in 17 of the 20 vitamin D-insufficient patients and was associated with significant (P < .02) 3.0% and 2.7% increases in BMD at the lumbar spine and the femoral neck, respectively. Failure to normalize the serum 25-OHD level was associated with further loss of BMD.ConclusionVitamin D insufficiency was the most frequently identified cause of bone loss in patients with declining BMD during bisphosphonate therapy. Correction of vitamin D insufficiency in these patients led to a significant rebound in BMD. (Endocr Pract. 2008; 14:293-297)     

Iatrogenic Osteoporosis,Bilateral Hip Osteonecrosis,and Secondary Adrenal Suppression in an Hiv-Infected Man Receiving Inhaled Corticosteroids and Ritonavir-Boosted Highly Active Antiretroviral Therapy

ObjectiveTo report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy.MethodsWe describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature.ResultsA 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy.Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma.ConclusionsGiven the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavirboosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression. (Endocr Pract. 2011;17:74-78)     

Management of Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease

ObjectiveTo review approved treatment options for secondary hyperparathyroidism (SHPT) in patients with stages 3 and 4 chronic kidney disease (CKD).MethodsRecently published data on the diagnosis and treatment of SHPT in patients with CKD were critically assessed.ResultsEarly detection of SHPT is critical for effective treatment. Approximately 40% of patients with stage 3 CKD and 80% of patients with stage 4 have SHPT due to low serum 1,25-dihydroxyvitamin D levels. Appropriate treatment involves suppression of parathyroid hormone (PTH) to normal levels with active vitamin D therapy and phosphate binders. Ergocalciferol or cholecalciferol should be used to correct 25-hydroxyvitamin D levels either before or during active vitamin D therapy. Active vitamin D analogues include calcitriol, doxercalciferol, and paricalcitol. Calcitriol is effective, but has a narrow therapeutic window at higher doses because of hypercalcemia and hyperphosphatemia, which require frequent monitoring. Doxercalciferol is also effective, but has been associated with significant elevations in serum phosphorus requiring greater use of oral phosphate binders. Paricalcitol effectively suppresses PTH with minimal impact on serum calcium and phosphorus. Limited data exist on the use of cinacalcet in treating SHPT in stages 3 and 4 CKD, and it is only approved for use in patients receiving dialysis.ConclusionSHPT is an early and major complication of CKD. Treatment involves suppression of PTH to prevent metabolic bone disease, bone loss, and metabolic complications that may result in marked morbidity and mortality. Early detection of elevated PTH levels with appropriate intervention using active vitamin D therapy, even in the absence of elevated serum phosphorus and reduced serum calcium, is critical. (Endocr Pract. 2008;14:18-27)     

New Treatment Modalities in Osteoporosis

ObjectiveTo describe recently discovered agents for the management of osteoporosis.MethodsA literature review (PubMed search) was conducted to identify agents at various stages of development for osteoporosis treatment. Agents under study or review for approval were included.ResultsIn menopause, bone remodeling is increased, and agents that suppress bone resorption can stabilize bone mass. In contrast, agents that target the osteoblast can increase bone formation and bone mass. Novel antiresorptive agents can target the formation or the activity of osteoclasts. They include denosumab, an antibody to receptor activated nuclear factor kB; new selective estrogen receptor modulators, such as bazedoxifene; and cathepsin K inhibitors, such as odanacatib. Src kinase inhibitors are in the early phases of development. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. Novel anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists. Recent discoveries have demonstrated that the Wnt/β-catenin signaling pathway has a central role in osteoblastic cell differentiation. Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. Anabolic therapies have the potential to enhance bone mass, but their long-term safety must be proven.ConclusionsNew developments in the treatment of osteoporosis include novel antiresorptive and anabolic agents. Their success will depend on their long-term effectiveness and safety profile. (Endocr Pract. 2010;16:855-863)     

Vitamin C Prevents Hypogonadal Bone Loss

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent.     

Identifying Parathyroid Hormone Disorders and their Phenotypes through a Bone Health Screening Panel: It's not Simple Vitamin D Deficiency!

Objectives: To determine the utility of bone health screening panels in identifying disorders of parathyroid gland secretions.Methods: A retrospective analysis of biochemical parameters in a bone health screening panel (BHSP) was conducted. Low and high cutoffs were applied to determine hypofunctioning and hyperfunctioning conditions related to parathyroid hormone. Clinical phenotypes of parathyroid gland abnormalities were determined using a combination of levels of calcium, 25-hydroxyvitamin D, and intact parathyroid hormone (iPTH). A PTH nomogram was applied to calculate the maximum expected PTH for existing levels of 25-hydroxyvitamin D. Medical records of patients were reviewed for clinical validation of biochemical findings.Results: Sixty-eight percent of subjects showed abnormal PTH secretion. Primary hyper- and hypoparathyroidism were detected in 1% (n = 5) and 0.4% (n = 2) of subjects, respectively. Normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high-normal PTH were identified in 8.5% (n = 37) and 2% (n = 10) of subjects, respectively. All subjects with primary and normocalcemic hyperparathyroidism had higher measured PTH than calculated maximum PTH using the PTH nomogram. Secondary hyperparathyroidism and functional hypoparathyroidism were present in 18% (n = 88) and 39% (n = 194) of subjects, respectively. High prevalence of bone pains, renal stones, and low bone mineral density were identified in patients with abnormal PTH secretion.Conclusion: Panel testing is useful in early diagnosis of metabolic bone disorders related to PTH. A BHSP helps identify normocalcemic hyperparathyroidism and hypercalcemia with inappropriately high PTH.Abbreviations:25OHD = 25-hydroxyvitamin DAKUH = Aga Khan University HospitalBHSP = bone health screening paneliPTH = intact parathyroid hormonemaxPTH = maximum parathyroid hormoneMBD = metabolic bone diseaseNCHPT = normocalcemic hyperparathyroidismPHPT = primary hyperparathyroidismPTH = parathyroid hormoneSHPT = secondary hyperparathyroidismVDD = vitamin D deficiency     

New Horizons in Skeletal Physiology and Pathophysiology

ObjectiveTo review new discoveries that revisit our current thinking on the genesis of osteoporosis using hypogonadal and thyrotoxic bone loss as examples.MethodsWe focus on cell biologic, mouse genetic, and human studies that have established a direct action of the interior pituitary hormones follicle-stimulating hormone and thyrotropin on the skeleton and discuss emerging clinical evidence for a novel pituitary-bone axis in humans that bypasses master endocrine organs, namely the ovaries and thyroid gland.ResultsThe cataloguing of human mutations, the use of genetically modified mice that recapitulate human disease, and the rapid growth of genomic sciences have together had a profound impact on how basic research is translated into clinical practice. The skeleton has become a paradigm for the application of such advances to an extent that hitherto unrecognized physiologic and pathophysiologic findings have emerged. We propose that hypogonadal and thyrotoxic bone loss are not solely due to changes in the level of master hormones, but instead also arise from the direct action of anterior pituitary hormones on the skeleton.ConclusionsWe predict a pituitary-bone axis in which pituitary hormones bypass traditional endocrine targets to affect the skeleton directly with remarkable sensitivity. New therapeutic targets thus become a likely possibility. (Endocr Pract. 2010;16:874-881)