BMJ, Iversen L, Bygum A. 363: k4882, 2018, with permission from BMJ Publishing Group Ltd. |
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zoledronic acid. 3 There is a risk of atypical femoral fractures, particularly with increasing duration of use. While very low with treatment of less than five years’ duration( fewer than one in 1000), this rises to around one in 250 in Caucasian women and as high as one in 50 in Asian women after 10 years of treatment. 5
This risk declines with cessation of therapy. As a result, a drug holiday may be considered in those receiving long-term bisphosphonate therapy. Decisions about treatment pauses must be individualised, weighing the risk – benefit profile for the patient, and warrant close supervision and BMD monitoring. 6
Denosumab is a human monoclonal antibody, inhibiting receptor activator of nuclear factor-kappa B( RANK)-ligand binding to its receptor, which in turn disrupts osteoclasts to decrease bone resorption and increase bone mass. It significantly reduces the risk of vertebral, non-vertebral and hip fractures in postmenopausal women and improves BMD in men with low bone density. 3, 4
It is administered via SC injection every six months.
A key potential adverse effect to consider is an increased risk of multiple vertebral fractures within 3 – 18 months of stopping denosumab treatment. This is due to rapid decrease in BMD and loss of vertebral fracture protection. Patients must be carefully counselled about the importance of maintenance treatment and the need for advanced planning and potential commencement of an alternative agent before cessation. 7
Teriparatide is a parathyroid hormone analogue, administered as a daily SC injection for up to 24 months. It increases bone density in men and postmenopausal women with osteoporosis and decreases fracture risk in postmenopausal women with osteoporosis. 3 Currently, PBS listing is limited to specialist physician prescribing for patients with severe osteoporosis, a T-score of-3.0 or less with two or more minimal trauma fractures, including one symptomatic fracture on antiresorptive therapy. Teriparatide is not recommended for patients with hypercalcaemia,
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previous radiation therapy to the skeleton, skeletal malignancies or bone metastases. Use is limited to 18 – 24 months because of theoretical concerns about increased rise of osteosarcoma. Upon discontinuing therapy, switching to a bisphosphonate or denosumab is associated with preservation of or increase in BMD.
Romosozumab is a monoclonal antibody that increases bone formation and reduces bone resorption by inhibiting sclerostin: a protein that reduces osteoblast function and bone formation. It is administered monthly via SC injection. The absolute risk reduction with romosozumab compared with bisphosphonate treatment is in the order of 1 – 1.3 % fewer fractures per year. Increasing evidence shows that the potent anabolic effect of this agent makes it the best choice of initial therapy for those with severe osteoporosis, followed by a sequential antiresorptive therapy. 3
Currently, romosozumab is PBS listed only for those with severe osteoporosis( T-score: ≤ – 3.0) who have sustained fractures despite antiresorptive therapy and must be prescribed by a specialist physician for no more than 12 months.
There is a potential increase in cardiovascular risk with romosozumab, so it should be avoided in patients with a history of MI or stroke. 3
Typically, a progress bone densitometry scan is performed at 12-24 months following diagnosis to assess initial response to treatment, with serial scans at two- to three-yearly intervals. An earlier scan is clinically indicated in some settings, such as if the patient experiences a fracture on treatment.
Barriers to treatment of osteoporosis include concerns about side effects, poor co-ordination and communication between health teams after an initial fracture and treatment costs. Fracture liaison services can be an effective strategy to identify patients with a recent fragility fracture and deliver a multidisciplinary intervention to optimise education and lifestyle management, assess fracture risk and consider pharmacotherapy to reduce fracture risk. 8
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Pharmacological options should be considered in those at high risk of minimal trauma fracture. |
What is the most likely diagnosis?
a Phytophotodermatitis
b Diabetic dermopathy
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c Actinic keratoses
d Flagellate dermatitis
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References on request from kate. kelso @ adg. com. au |
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ANSWER The answer is b. Diabetic dermopathy( also known as shin spots or pigmented pretibial patches) occurs in up to 50 % of patients with diabetes, most commonly in those with microangiopathic complications. 1-3
The typical presentation is with multiple asymptomatic, round, dull red to pink papules or plaques predominantly located on the pretibial skin. Lesions evolve over 1-2 weeks to form well-circumscribed, atrophic, indented brown macules and patches. There may be associated fine scale. 1
Diabetic dermopathy is usually seen in those with diabetes of at least 10 years’ duration, and is closely linked to increased HbA1c. 3 The pathophysiology of the condition is unclear, but given the typical location on bony areas( usually both shins, and occasionally the forearms), it is hypothesised that it may represent a magnified response to injury or trauma. 1
Diagnosis is clinical, with a skin biopsy warranted only in cases of diagnostic uncertainty. There is no treatment for diabetic dermopathy apart from management of dysglycaemia, with improvement or resolution expected, particularly in the setting of better glycaemic control.
Phytophotodermatitis, a form of plant dermatitis, may present with linear or streaked pigmented patches in the distribution of exposure of skin to plant sap and fruit, followed by sun exposure. In this case this diagnosis is less likely, given the patient typically keeps his legs covered in higher risk settings for exposure( ie, when working outdoors). Flagellate dermatitis is a distinctive streaky linear rash that can occur after ingestion of raw or undercooked shiitake mushrooms. It is characterised by pruritic, erythematous, linear streaks, which may be exacerbated by sun exposure and be associated with acute gastrointestinal symptoms. It typically resolves within weeks.
Dr Kate Kelso is a GP and medical editor at Australian Doctor. References on request from kate. kelso @ adg. com. au
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