Bone: Fracture risk after bariatric surgery

David Holmes

Nature Reviews Endocrinology

Patients with severe obesity who undergo bariatric surgery are at increased risk of fractures, according to a new study published in the British Medical Journal. The findings seem to contradict the widely-held notion of obesity being protective against fractures.

Opinion: Vitamin D and falls — the dosage conundrum

J. Christopher Gallagher

Nature Reviews Endocrinology

Falls are a major health problem in elderly individuals. Although intensive physical therapy and management of hazards in the home can reduce falls by 25%, long-term practicality limits their use. Interest in vitamin D as a medical therapy has led to many trials; however, results using daily oral doses of vitamin D have been inconsistent. In the past 5 years, studies on the effect of bolus doses of vitamin D have produced surprising results. Bolus doses of vitamin D, given annually (at a dose of 300,000 IU or 500,000 IU) or monthly (at a dose of 24,000 IU or 60,000 IU) — equivalent to approximate daily doses of 800 IU, 1400 IU and 2,000 IU — result in a significant increase in the number of falls and fractures associated with serum levels of 25-hydroxyvitamin D greater than 40–45 ng/ml (equivalent to 100–112 nmol/l). These unexpected results show increased falls and fractures are adverse events related to vitamin D administration. Until further safety data is available, bolus dosing or daily doses should not exceed 3,000 IU and serum levels of 25-hydroxyvitamin D should not exceed 40–45 ng/ml (equivalent to 100–112 nmol/l) in elderly individuals.

Exercise: Osteocalcin in the adaptation to exercise

Claire Greenhill

Nature Reviews Endocrinology

A bone hormone, osteocalcin, is required for adaptation to exercise and optimum exercise capacity, according to new research published in Cell Metabolism.

Bone diseases: Dual sclerostin–DKK1 antibody outperforms monotherapy

David Holmes

Nature Reviews Endocrinology

The Wnt antagonist Dickkopf-1 (DKK1) is part of a negative feedback mechanism that limits the effect of sclerostin inhibition on bone mass accrual, according to new research published in Nature Communications. The findings could explain the declining bone-forming activity of sclerostin antibodies observed during chronic monotherapy.

Bone: Does anti-sclerostin therapy promote inflammation in rheumatoid arthritis?

Natalie A. Sims

Nature Reviews Endocrinology

One of the most promising new approaches currently in clinical trials for postmenopausal osteoporosis is the promotion of bone formation by antibodies directed against the Wnt inhibitor, sclerostin. A new study by Wehmeyer and colleagues suggests that this approach might have a pro-inflammatory effect in patients with tumour necrosis factor (TNF)-dependent rheumatoid arthritis.

Bone: Cranking fracture repair up a notch

Tim Geach

Nature Reviews Endocrinology

Bone marrow stem cells (BMSCs) are important for skeletal development, but their role in bone repair after fracture is unclear. In new data presented in The Journal of Clinical Investigation, Notch signalling within BMSCs is shown to be required for the complete repair of fractures.

Osteoporosis: Not all BMD is created equal

Joana Osório

Nature Reviews Rheumatology

Antiresorptive and anabolic therapies have different effects on bone mineralization density distribution (BMDD), a measure of the distribution of calcium concentration across the bone matrix. This finding was reported by David Dempster and colleagues in the Journal of Bone and Mineral Research.

Therapy: New findings on vitamin D₃ supplementation and falls — when more is perhaps not better

Kerrie M. Sanders & Markus J. Seibel

Nature Reviews Endocrinology

Results from a recent randomized controlled trial on vitamin D₃ supplementation suggest that even modestly high doses of vitamin D₃, when given once monthly, might be associated with an increased rate of falls in older people. These findings support the conservative approach of the Institute of Medicine's recommendations of 800 IU of vitamin D₃ per day for older adults.

Bone: The circadian clock controls bone remodelling

Liesbet Lieben

Nature Reviews Rheumatology

A new study published in Bone reveals that the regulation of bone homeostasis by the circadian clock is more complex than previously thought.

Bone: Antiresporpive agents benefit glucococorticoid users

Caroline Barranco

Nature Reviews Rheumatology

A network meta-analysis of 27 randomized controlled trials shows that antiresorptive therapy does reduce the incidence of vertebral fracture in patients receiving oral glucocorticoids.

Bone: New spine BMD loci associated with fractures

David Holmes

Nature Reviews Endocrinology

A novel BMD locus within PTCH1, which encodes protein patched homologue 1 (the receptor for three Hedgehog morphogens), is associated with reduced BMD at the spine (P = 1.0 × 10⁻¹¹) and an increased risk of osteoporotic fractures (P = 8.5 × 10⁻⁴, OR = 1.09), according to a new study published in Nature Communications.

Bone: Autophagy regulates bone growth in mice

Claire Greenhill

Nature Reviews Endocrinology

The secretion of type II collagen in growth plate chondrocytes is regulated by autophagy, according to newly published results. Furthermore, the study demonstrated that autophagy is regulated by a growth factor signalling pathway.

Inflammation: Immune recovery drives bone loss

David Holmes

Nature Reviews Endocrinology

HIV infection is associated with loss of bone mass and an increased incidence of fractures, which are exacerbated by antiretroviral therapy (ART) during the first 2 years of treatment. A new study shows that reconstitution of the T-cell population in immunocompromised mice (mimicking ART-induced T-cell expansion and immune activation) recapitulates the bone loss observed with ART.

Bone: Irisin boosts bone mass

David Holmes

Nature Reviews Endocrinology

The myokine irisin, which is produced by skeletal muscle in response to exercise, increases both the mass and strength of cortical bone, according to a new study. The findings provide a possible explanation for the beneficial effects of physical activity on the skeleton triggered by skeletal muscle.

Bone: Antifracture efficacy of growth hormone — confirmation at long last

David Holmes

Nature Reviews Endocrinology

Growth hormone (GH) treatment reduces the long-term risk of fractures in women with postmenopausal osteoporosis, according to a new study.