Osteoporosis

Phosphorous balance in chronic kidney disease

Phosphorous balance in chronic kidney disease

In the setting of chronic kidney disease, elevated blood phosphorous levels can increase the risk of death, in addition to cardiovascular, parathyroid and bone disorders. This case shows us that the other extreme is also dangerous: severe oral phosphorous restriction and severe hypophosphatemia lead to profound muscle weakness, ostemalacia, osteoporosis and multiple bone fractures. Arisotle's aurea mediocritas applies nicely here too.

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New FDA approval: the first drug for x-linked hypophosphatemia

New FDA approval: the first drug for x-linked hypophosphatemia

Crysvita or burosumab is the first drug to be approved by FDA for treatment of x-linked hypophosphatemia in adults and children older than one year of age. It is inherited, rare and unresponsive to vitamin D supplementation. It is a form of ricket and osteomalacia leading to low blood phosphorus levels.  Clinical manifestations are disabled bone growth and development in children and impaired bone mineralization in adults.

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Mineral bone disorder in the setting of kidney disease.

Mineral bone disorder in the setting of kidney disease.

This is a nice summary of the latest guidelines on diagnosis and management of mineral bone disease induced by chronic kidney disease. Kidney anomaly can be classified functionally via estimated GFR or structurally via proteinuria.

Guidelines emphasize the need for bone density scan, bone biopsy, parathyroid hormone, calcium and phosphorus measures in the right context. Vitamin D analogs and phosphate binders are also discussed. See below for detailed recommendations.

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"Identify first, then intervene" paradigm is confirmed for hip fractures

"Identify first, then intervene" paradigm is confirmed for hip fractures

Despite effective assessment methods and medications targeting osteoporosis and related fractures, screening for fracture risk is not currently advocated in the UK. Study tested whether a community-based screening intervention could reduce fractures in older women.

Results showed that systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures.

Lancet

New osteoporosis drug (romosozumab) performs better than fosamax

New osteoporosis drug (romosozumab) performs better than fosamax

Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone.

NEJM

How to treat diabetes in the context of osteoporosis

How to treat diabetes in the context of osteoporosis

This is a nice review of literature on how to approach diabetes management in the setting of osteoporosis. Metformin, DPP4-inhibitors and GLP1-agonists are preferred medications. Insulin and sulfonylurea can cause hypoglycemia leading to confusion, falls, and eventually fractures.  Pioglitazone and invokana can directly contribute to worsening of osteoporosis. The effects of jardiance and farxiga on the bone are less clear. Insulin is recommended for hospitalized patients as they are monitored closely. On the other hand, osteoporosis treatment should not be swayed by diabetes status or management. 

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New FDA approval: Tymlos (abaloparatide) for Osteoporosis

New FDA approval: Tymlos (abaloparatide) for Osteoporosis

In April 2017, FDA approved Tymlos/AbaloParatide for treatment of postmenopausal osteoporosis. Tymlos has potent bone anabolic properties (PTH1 receptors). It is administered once a day subcutaneously for up to 2 years. Side effect could be nausea and palpitations. The original study published in JAMA June 2016 suggests overall tymlos superiority over forteo in fracture reduction and bone density improvement during an 18 month observation.

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Estradiol and Testosterone vs. Bone Fractures in Women

Estradiol and Testosterone vs. Bone Fractures in Women

The study shows that higher levels of estradiol (E2>0.82 ng/dL) and testosterone (T>13.3 ng/dL) are associated with lower chance of non-vertebral fractures. Risk reduction was as low as 44%. Should postmenopausal women be risk stratified by measuring serum E2 and T levels?

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Osteoporotic Drugs in Kidney Disease, who knows?

Osteoporotic Drugs in Kidney Disease, who knows?

This systematic review and meta-analysis included 13 randomized clinical trials from 2006-2016. Bisphosphonates, teriparatide (forteo), raloxifene, and denosumab (prolia) were compared with non-pharmacological therapy in patients with kidney disease: transplant, dialysis or simply stage 3-5. No clear benefit or harm of antiosteoporotic agents was found in individuals with CKD.

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Osteoporosis Guidelines, an ACP Update 2017

Osteoporosis Guidelines, an ACP Update 2017

The recent ACP update on osteoporosis guidelines is shown below. Interestingly, American College of Physicians recommends against the use of DEXA/bone scans for treatment surveillance; although evidence quality is low for such an advice. Recommendations are listed with slight modified wording for easier and succinct reading.

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Aldosterone & Vertebral Fractures

Aldosterone & Vertebral Fractures

Elevated autonomous aldosterone production is more common than previously believed. Primary aldosteronism is estimated to cause "essential" and resistant hypertension in up to 10% and 20% of adults. These numbers are significant given wide prevalence of high blood pressure in the general population.

This original study suggests that primary aldosteronism is also a unique contributor to vertebral fracture, raising its risk by 3 fold. Authors hypothesize that excessive aldosterone causes fracture by reducing bone quality rather than bone density. A partial effect could also be its ability to increase urinary calcium excretion in the distal tubule.

Important to note the association of hyperaldosteronism with metabolic syndrome, higher A1c and Triglycerides and lower HDL.

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Concerning: Prolia discontinuation could lead to severe rebound vertebral fractures

Concerning: Prolia discontinuation could lead to severe rebound vertebral fractures

Prolia was FDA approved in June 2010 for treatment of osteoporosis. It prevents bone resorption leading to increased bone density and fracture prevention. It is a human monoclonal antibody targeting RANK Ligand, ultimately diminishing osteoclast formation and function.

The article describes case reports of rebound vertebral fractures soon after prolia discontinuation. Further studies are needed to quantify prevalence and identify other contributing factors.

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