Toranomon Hospital Endocrine Center

Toranomon Hospital Endocrine Center

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Vitamin D plays a pivotal role in the regulation of bone metabolism, essentially through its effects on calcium and phosphate absorption. Although major targets of vitamin D action are skeletal system and mineral metabolism, vitamin D receptor is ubiquitously expressed in many tissues. Accumulating evidence suggests a possible involvement of vitamin D in the regulation of blood sugar and blood pressure in addition to its effects on bone and mineral metabolism.


Takeuchi Y.,Toranomon Hospital Endocrine Center
Clinical calcium | Year: 2013

Accumulating evidence clearly indicates both thyroid hormone and estrogen have a pivotal role in bone metabolism. Pituitary hormones, TSH and FSH, regulate circulating levels of thyroid hormone and estrogen, respectively. Recent works raise a possibility that either TSH or FSH also has its own direct effects on bone cells involved in bone resorption and formation. More recently, it is suggested that oxytocin and vasopressin are also involved in bone metabolism. However, several investigations of genetically manipulated model mice and clinical data from patients with certain diseases have provided inconsistent results. Thus, we need more data that answer the question whether or not each pituitary hormone is physiologically and pathophysiologically involved in controlling bone metabolism in human.


Takeuchi Y.,Toranomon Hospital Endocrine Center
Clinical calcium | Year: 2012

Patients with either type 1 or type 2 diabetes mellitus (DM) are predisposed to fragile fracture. In particular, although bone mineral density in patients with type 2 DM is somewhat higher than control subjects, diabetic patients are more likely to break a bone. Because the number of elderly patients with DM is getting larger, it is necessary to prevent fracture in those. Unfortunately, substantial randomized control trials are yet to be done in patients with DM to clarify if anti-osteoporotic drugs are effective to prevent fractures. According to post-hoc analyses of pivotal clinical studies of alendronate and raloxifene, best available clinical data at the present time, those anti-osteoporotic drugs seem to be equally effective in diabetic patients to controls. We are now waiting for evidence of effects of teriparatide and other drugs on patients with DM.


Many medications can increase fracture risk. Osteoporosis is classified as either primary or secondary. Drug-induced osteoporosis is a type of secondary osteoporosis. Glucocorticoids are the most common cause of drug-induced osteoporosis. But other drugs can increase fracture risk, such as thyroxine overdose, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors, thiazolidines, proton pump inhibitors, loop diuretics, anticoagulant drugs, selective serotonin reuptake inhibitors (SSRI) , tricyclic antidepressants, anticonvulsant, and so on. This review will discuss clinical trials and the mechanisms underlying drug-induced fracture.


Takeuchi Y.,Toranomon Hospital Endocrine Center
Clinical calcium | Year: 2014

Oral bisphosphonates are the first class of drugs other than estrogen that have been proven to reduce fracture incidence substantially. Since they are agents that inhibit bone resorption and are hardly absorbed through intestine, researchers have been focusing on augmentation of inhibitory effects of bisphosphonates on bone resorption and prolongation of the interval of drug administration. Even though they have a break-through efficacy on preventing fractures, there remain some rare problems to be solved, such as osteonecrosis of the jaw and atypical femoral fracture, after long-term exposure to bisphosphonates.


Suzuki H.,Toranomon Hospital Endocrine Center
Clinical calcium | Year: 2015

Bone complication occurs in patients with alcoholic hepatitis, chronic hepatitis C, primary biliary cirrhosis(PBC), primary sclerosing cholangitis(PSC)or post liver transplant. Prevalence of osteoporosis and fracture risk is high in these diseases. Nonalcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)is increasing in prevalence. Relation of NAFLD/NASH with osteoporosis, however, is not well known, and further investigation is needed.


Suzuki H.,Toranomon Hospital Endocrine Center
Clinical calcium | Year: 2012

PTH increases bone formation and has an anabolic effect on bone. Antiresorptive drugs such as bishopshonateand selective estrogen receptor modulator (SERM) inhibit bone resorption and increase bone mineral density (BMD) . Efficacy of combinationtreatment with PTH and antiresorption drugshas been investigated. It has been reported that single intravenous infusion of zoledronic acid along with daily subcutaneous injection of PTH (1-34) (teriparatide) increases both spine and hip BMD. On the other hand, daily oral alendronate and daily PTH (1-84) showed no additive effects. Patients who had been treated with antiresorption drugs showed somewhat blunt but significant positive response to teriparatide. It warrants sequential therapy with teriparatide following antiresorption drugs that is common in daily practice of osteoporosis. Since a period of PTH administration is limited up to 24 months and bone mineral density starts to decreases shortly after discontinuation of PTH, sequential treatment with antiresorptive agents following PTH is highly recommended.


Accumulating evidence indicates that several drugs for lifestyle-related diseases are involved in bone metabolism. Drugs that might reduce fracture incidence are statins, β-blockers and thiazide diuretics, and those that might increase fractures are thiazolidinediones and loop diuretics. It is yet controversial whether ACE inhibitors, angiotensin receptor- II blockers and aldosterone receptor antagonists in addition to incretin-related drugs are indeed involved in the increase or the decrease in fracture incidence.


Eldecalcitol, a newly developed active vitamin D3 analogue, has an inhibitory effect on bone resorption through disruption of osteoclast formation. In a double blind randomized controlled trial in Japanese patients with osteoporosis, eldecalcitol has been shown to increase bone mineral density and to decrease the incidence of vertebral fractures more effectively than alfacalcidol, an authentic active vitamin D3 analogue for treatment of osteoporosis. In general, long-term use of eldecalcitol seems to be safe ; however, it occasionally might develop hypercalcemia and serious renal impairment as does alfacalcidol. To prevent the adverse event, serum calcium and creatinine levels should be monitored routinely during the treatment with eldecalcitol.


Takeuchi Y.,Toranomon Hospital Endocrine Center
Clinical calcium | Year: 2014

Teriparatide is an only available bone anabolic drug in practice. It is a N-terminal fragment of parathyroid hormone (PTH) . Mode of actions of teriparatide is pharmacological but not physiological as it is administered to patients with osteoporosis. Physicians need to understand the fact that treatment with teriparatide is not just like a hormone replacement. They also should administer teriparatide to their patients after rigorous evaluation of its clinical superiority to other anti-osteoprosis drugs, because it is not classified as a first-line drug.

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