Paget's disease clinical guidelines

the Endocrine Society just released clinical practice guidelines for the diagnosis and management of Paget's disease of the bone (see pagets clin pract guideline endo society 2014 in dropbox, or go to URL: http://press.endocrine.org/doi/pdf/10.1210/jc.2014-2910 ). some background: there is a genetic component with family history in 10-20% and autosomal dominant transmission pattern, clinically rare prior to age 40, men and women affected. basic recommendations:

Diagnosis
--in patient with suspected paget's, get plain xray of suspected area. if diagnosed with paget's, then get radionuclide bone scan to assess extent of disease
--if diagnosed with paget's by xray, get biochemical evaluation: alkaline phosphatase (ALP) or more specific marker of bone formation (especially if there is hepatobiliary disease which could affect the ALP) – can check amino-terminal propeptide of type 1 collagen (P1NP, the best option but expensive) or bone-specific ALP (though there is about 20% cross-reactivity between antibodies to liver and bone ALP) and bC-terminal propeptide of type 1 collagen (bCTx) or urinary N-terminal propeptide of type 1 collagen (NTx).

Treatment
--bisphosponates if at risk of future complications
--"suggest" a single 5-mg dose of IV zolendronate as treatment of choice, since it usually lasts >6 years and requires less costly followup. other options include alendrontate 40mg/d for 6 months (may need to retreat in 2-6 years) or risedronate 30 mg for 2 months (may need to retreat in 1-5 years)
--if symptoms need to be controlled urgently (see below), assess markers of short-term response to assess if there is adequate response to therapy (here it is best to use b​CTx as marker of bone resorption, since it responds more rapidly to treatment than ALP). assess before and shortly after treatment initiation
--if osteolytic lesions present, repeat xray in 1 year
--maintaining remission: check ALP or other baseline disease markers at 6-12 weeks after theapy, though maximal suppression may take 6 months. follow bone turnover markers (should be below midpoint of assay reference range) as marker of need for retreatment. for zolendronate, check every 1-2 years. for other regimens, check every 6-12 months.
--monostotic paget's:  all of the biochemical markers of bone turnover may be normal even in symptomatic patients

Complication Management
--hearing loss: treat with potent bisphosphonate (eg IV zolendronate) to prevent worsening
--osteoarthritis: if severe, bisphosphonates (even before joint replacement surgery).  when mild, use analgesics. often hard to know if it is the paget's or underlying osteoarthritis causing the pain. can consider bisphophonates as well as analgesics, though data sparse.
--bowing of lower extremity: potent bisphosphonate (eg IV zolendronate)​ prior to surgery
--paralysis (with disease of the spine): bisphosphonate with neurosurgical evaluation. usually medical therapy is sufficient (unless severe structural damage)
--neoplasm: if osteosarcoma or giant cell tumor, pretreat with  potent bisphosphonate prior to surgery. interesting that neoplasms seem to be less frequent in this era of bisphosphonates.

in reviewing financial disclosures, of the 7 members of the taskforce, 2 without conflict, 1 with declared conflicts, and 4 with financial interests in several drug companies but stated that there were no conflicts.