Bone turnover decreases and bone structure improves during treatment with weekly high-dose methylprednisolone for 12 weeks in Graves' orbitopathy.

PURPOSE: Weekly treatment with the intravenous glucocorticoid methylprednisolone for 12 weeks is mainstay in the treatment of Graves' orbitopathy but may decrease bone mass and impair bone structure. We therefore investigated bone turnover, -mass and -structure during the treatment cause in these patients. METHODS: We included 32 patients with Graves' orbitopathy scheduled for treatment with methylprednisolone. Bone turnover and thyroid function was measured at baseline and after 3, 9, 12, and 24 weeks, bone mineral density (BMD) was measured using dual x-ray absorptiometry at baseline and after 12 and 24 weeks, and bone structure was measured using high-resolution peripheral quantitative computed tomography at baseline and after 12 weeks. RESULTS: Bone turnover and tri-iodothyronine decreased throughout the study. Cortical volumetric BMD at both the radius and tibia increased significantly by 0.98 ± 0.38% (p = 0.01) and 1.35 ± 0.50% (p = 0.01), respectively and cortical porosity at both the radius and tibia decreased significantly by -7.67 ± 3.13% (p = 0.04) and -3.30 ± 2.17% (p = 0.04), respectively. Bone mineral density was stable during the first 12 weeks but increased significantly by 2.26 ± 3.61% at the femoral neck (p < 0.01) and by 2.24 ± 4.24% at the total hip towards week 24 (p = 0.02). Stratified analyses suggested that remission of hyperthyroidism was the most important determinant of changes in bone turnover, bone mass and structure. CONCLUSION: During a 12-week course of high-dose intravenous methylprednisolone bone turnover and cortical porosity decreased and during 24 weeks follow up bone mineral density increased. In terms of bone, methylprednisolone therefore is a safe treatment for Graves' orbitopathy.

The risk of osteoporosis in patients with asthma.

It is well-known that use of continuous systemic corticosteroids (SG) affects bone metabolism, bone mineral density (BMD), and ultimately increases the risk of osteoporosis. In patients with asthma, on the other hand, the effects of long-term high-dose inhaled corticosteroids (ICS) on BMD and risk of osteoporotic fractures is controversial. The reasons for this inconsistency could be explained by the fact that only few long-term studies investigating the effect of ICS in patients with asthma exist. The studies are characterized by different study designs and duration of ICS exposure, small study populations, and differences between the used ICS. The aim of this article is to unravel which factors, if any, that contribute to an increased risk of osteoporosis in patients with asthma and to summarize the evidence regarding adverse effects of ICS on bone metabolism, BMD and osteoporotic fractures in patients with asthma.

Huge variations in definition and reported incidence of postsurgical hypoparathyroidism: a systematic review.

PURPOSE: The reported incidence of post surgical hypoparathyroidism (HypoPT) varies greatly. Previous research suggests that the definition of HypoPT is not consistent in the literature. We therefore conducted a systematic review to investigate how HypoPT is defined and whether this definition, as well as the selected threshold for hypocalcemia affects the incidence. METHODS: Using a predefined search string we identified all articles in PubMed reporting on the incidence of postsurgical HypoPT from 1st January 2010 to January 2017. RESULTS: We identified 89 articles that employed 20 different definition of HypoPT. The incidence of HypoPT varied from 0.0% to 20.2%. The definitions were not associated with incidence of HypoPT. Use of prophylactic post-operative calcium supplements, however decreased the risk of HypoPT (p = 0.03), and there was a trend towards a lower risk of HypoPT when using a definition of hypocalcemia below lower limit of the reference range (p = 0.09). CONCLUSION: The large number of definitions of HypoPT, as well as the huge variation in incidence point to a problem suggests that the awareness of HypoPT should be raised. Use of prophylactic post-operative calcium supplements may decrease risk of HypoPT. This, however, may be due to reverse causality as awareness of the risk of HypoPT may promote the use of calcium supplementation.

[Phytoestrogens as a dietary supplement].

Phytoestrogens (PE) are widely used as a dietary supplement. PE affect oestrogen receptors. PE have been investigated regarding menopausal hot flushes, bone mineral density and prostate hyperplasia/cancer. It seems consistent, that PE increase bone mineral density, whereas the effect on hot flushes is controversial. Due to the effect on oestrogen receptors, concerns exist on the risk of cancer and venous thromboembolism related to the intake of PE. To date, no studies with PE have been large enough to clarify their safety. Widespread use of PE should therefore be discouraged.

Long-Term High-Dose Resveratrol Supplementation Reduces Bone Mass and Fracture Strength in Rats.

Resveratrol (RSV) is a natural polyphenolic compound. A recent study suggests a positive effect on BMD in men; however, the underlying changes in microstructure and strength remain unknown. We aimed to investigate the effects of RSV on the skeleton in hindlimb-immobilized and non-immobilized rats. Seventy-two female Wistar rats were divided into six groups. Two baseline (BSL) groups underwent short-term diet intervention for 4 weeks before sacrifice [phytoestrogen-deficient diet (PD) (BSL + PD) or RSV diet (600 mg/kg body weight/day) (BSL + RSV)]. Four groups were injected in the right hindlimb with botulinum toxin (BTX) (immobilized) or saline (non-immobilized), and fed either PD diet or RSV diet 4 weeks pre-injection and 6 weeks post-injection before sacrifice (BTX + PD, BTX + RSV, PD, and RSV, respectively). DXA, µCT, dynamic histomorphometry, and mechanical tests were performed. Short-term RSV treatment did not affect bone parameters, whereas long-term RSV exposure had a consistent negative impact on non-immobilized rats (RSV vs. PD); whole femoral aBMD (p = 0.01) and distal femoral metaphyseal Tb.N (p = 0.01), Tb.Sp (p = 0.02), and BV/TV (p = 0.07). At the femoral mid-diaphysis, RSV increased periosteal resorption (p = 0.01) and increased endosteal formation (p = 0.02), while mineralization was unaffected. In addition, RSV reduced femoral mid-diaphyseal three-point bending strength (p = 0.03) and stiffness (p = 0.04). BTX-induced immobilization resulted in significant bone loss and reduced bone strength; however, RSV supplementation was unable to prevent this. In conclusion, long-term high-dose RSV reduced bone mass and fracture strength and did not prevent immobilization-induced bone loss in rats.

Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women.

OBJECTIVE: Clinical studies suggest that vitamin K2 protects against bone loss and fractures; however, its effect on bone quality has never been investigated. We investigated the effect of vitamin MK-7 on undercarboxylated osteocalcin (ucOC), and bone mass and quality. DESIGN: We conducted a randomised, placebo-controlled, double-blinded clinical trial. METHODS: We investigated the effect of MK-7 375 µg for 12 months on bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA), bone microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) and biochemical bone turnover markers in 148 postmenopausal women with osteopenia. All of them were supplemented with calcium and vitamin D. RESULTS: ucOC decreased in the MK-7 group (-65.6 (59.1; 71.0) %) (median (CI)) compared with the placebo group (-6.4 (-13.5; 1.2) %) after 3 months (P < 0.01). HRpQCT after 12 months demonstrated that trabecular number in tibia was unchanged in the MK-7-group (-0.1 ± 1.9%) (mean ± s.d.) and decreased in the placebo group (-3.5 ± 2.2%), trabecular spacing was unchanged in the MK-7 group (+1.2 ± 8.0%) and increased in the placebo group (+4.5 ± 9.7%), and trabecular thickness was unchanged in the MK-7 group (+0.2 ± 1.7%) and increased in the placebo group (+4.0 ± 2.2%) (between-group changes for all: P < 0.05). There were no significant differences between the groups in HRpQCT-derived parameters at the radius or in BMD at any site. CONCLUSION: The changes in bone microarchitecture in the placebo group are consistent with the age-related deterioration of trabecular structure, with a loss of trabeculae and a greater mean thickness of the remaining trabeculae. This suggests that vitamin MK-7 preserves trabecular bone structure at the tibia.

Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial.

CONTEXT: Metabolic syndrome (MetS) is associated with low-grade inflammation, which may harmfully affect bone. Resveratrol (RSV) possesses anti-inflammatory properties, and rodent studies suggest bone protective effects. OBJECTIVE: This study sought to evaluate effects of RSV treatment on bone in men with MetS. SETTING AND DESIGN: The study was conducted at Aarhus University Hospital as a randomized, double-blinded, placebo-controlled trial assessing changes in bone turnover markers, bone mineral density (BMD), and geometry. PARTICIPANTS: The study population comprised 74 middle-aged obese men with MetS recruited from the general community, of which 66 completed all visits. Mean age of participants was 49.3 ± 6.3 years and mean body mass index was 33.7 ± 3.6 kg/m(2). INTERVENTION: Oral treatment with 1.000 mg RSV (RSV(high)), 150 mg RSV (RSV(low)), or placebo daily for 16 weeks. MAIN OUTCOME MEASURE: Prespecified primary endpoint was change in bone alkaline phosphatase (BAP). RESULTS: BAP increased dose dependently with RSV (R = 0.471, P < .001), resulting in a significantly greater increase in BAP in the RSV(high) group compared with placebo at all time-points (week 4, 16.4 ± 4.2%, P < .001; week 8, 16.5 ± 4.1%, P < .001; week 16, 15.2 ± 3.7%, P < .001). Lumbar spine trabecular volumetric bone mineral density (LS vBMD(trab)) also increased dose dependently with RSV (R = 0.268, P = .036), with a significant increase of 2.6 ± 1.3% in the RSV(high) group compared with placebo (P = .043). In addition, changes in BAP and LS vBMD(trab) were positively correlated (R = 0.281, P = .027). No consistent changes were detected in bone density at the hip. CONCLUSIONS: Our data suggest that high-dose RSV supplementation positively affects bone, primarily by stimulating formation or mineralization. Future studies of longer duration comprising populations at risk of osteoporosis are needed to confirm these results.