most cases of primary hyperparathyroidism ( around 80 - 90% ) , are caused by an increased secretion of parathyroid hormone ( pth ) from a single adenoma . most studies have shown a higher incidence of primary hyperparathyroidism ( phpt ) among women than men , with the highest incidence in postmenopausal women . patients with normocalcemic ( normal calcium < 10.5 mg% ) hyperparathyroidism have more substantial skeletal involvement than is typical in primary hyperparathyroidism and develop more features and complications over time . up to 57% of the patients have osteoporosis , with significant bone loss , seen more frequently at the hip and forearm than at the spine . a 61-year - old , married lady , was referred to our endocrine clinic by a general practitioner , with a background of hypertension ( untreated , since four years ) and right hemi - thyroidectomy ( performed 15 years ago for multinodular goiter ) , with complaints of persistent lower backache ( non - radicular ) and generalized severe body ache that had worsened after she was put on teriparatide ( since four months ) . the teriparatide was started by the primary care physician for severe osteoporosis that was thought to be due to premature menopause ( achieved at the age of 35 years ) . she was a vegetarian , non - smoker , non - ethanolic without any significant family history or drug history . examination revealed a lady withdrawn in pain , weighing 61 kg , with a body mass index of 27.5 kg / m . the blood pressure was 160/92 mm of hg supine and 170/106 mm of hg when sitting , without any postural fall . the proximal muscle weakness was 4/5 in all four limbs . biochemistry was unremarkable , except for mild hyponatremia ( sodium 130 mmol / l ) and elevated alkaline phosphatase 140 iu / l ( 50 - 136 ) , which was associated with a corrected calcium of 9.7 mg / dl ( calcium 10.1 mg / dl , albumin 4.5 gm % ) and normal liver function . although teriparatide therapy could possibly have accounted for these changes , we chose to look at her previous results , with a suspicion of a possible secondary cause for the elevated high alkaline phosphatase on the background of worsening symptoms . it was noted that she had corrected calcium as high as 10.3 mg% on review of her previous results , which we thought was significantly elevated , especially as her diet was poor in calcium . further enquiry suggested large volumes of fluid intake ( free water ) approximately 4 - 5 liters / day , which the patient put down to persistent thirst , which we considered to be secondary to polydipsia . the adrenal and thyroid screen ( tsh : 1.14 miu / ml ) screen was normal subsequent specialized testing revealed an elevated parathormone 166 pg / ml ( 11 - 54 ) , insufficient vitamin d3 27 ng / l ( 11 - 42 ) , and hypercalciurea ( 24-hour urine calcium 624 mg % ( 50 - 300 mg% ) ) , and thus a pth - dependant etiology for hypercalcemia was considered . plain x - ray of the chest was normal . a s keletal survey revealed spondylolisthesis of l4 over l5 , without any obvious fractures . dual energy x - ray absorptiometry ( dexa ) densitometry showed a worsening t - score at the spine ( t - scores , hip  2.3 , spine  3.9 , forearm  4.5 ) , compared to the previous results . the echocardiogram was consistent with evidence of systemic hypertension showing diastolic dysfunction with mild concentric left ventricular hypertrophy . specialized imaging in the form of doppler ultrasound of the neck suggested a mass at the inferior pole of the right lobe of the thyroid gland ( most likely a parathyroid adenoma ) . the sestamibi scan confirmed the presence of a right inferior parathyroid adenoma as localized by ultrasonography . microscopy showed an encapsulated lesion composed of a diffuse proliferation of chief cells with surrounding delicate capillary network [ figure 1 ] . the patient continued to remain well with corrected calcium of 9.3 mg% , with a plan of yearly zolendronic acid infusions for a total of five infusions photomicrograph showing parathyroid adenoma ( h and e , 10 ) osteoporosis is a systemic skeletal disorder characterized by low bone mass and micro - architectural deterioration of the bone , with a consequent increase in bone fragility and susceptibility to fracture . previous prospective studies indicate that the risk of an osteoporotic fracture increases continuously as bone mineral density ( bmd ) declines , with a 1.5 to 3-fold increase in the risk of fracture for each standard deviation fall in the bmd most american women under the age of 50 have normal bmd , however , as many as 70% are osteoporotic at the hip , lumbar spine , or forearm by the age of 80 years . epidemiological studies from north america have estimated the remaining lifetime risk of common fragility fractures to be 17.5% for a hip fracture , 15.6% for a clinically diagnosed vertebral fracture , and 16% for a distal forearm fracture , among white women of age 50 years . a british study using the general practice research database estimated the lifetime risk of any fracture to be 53.2% at the age of 50 years among women and 20.7% at the same age among men teriparatide refers to the 1 - 34 n - terminal active fragment of the recombinant parathoromone , an osteoanabolic that has revolutionized the treatment of osteoporosis . it is indicated for use in postmenopausal women , men with idiopathic or hypogonadal osteoporosis , and in men or women with glucocorticoid - induced osteoporosis , with a bone mineral density lower than three standard deviations from normal . kung aw showed that vertebral bone mineral density values ( assessed at the lumbar spine ) significantly increased from baseline to a greater extent with teriparatide 20 ug / ml than with placebo , alendronate or calcitonin . in the fracture prevention trial , the bone mineral density was increased by 9% more in recipients of teriparatide teriparatide is licensed for use for approximately 18 months and not longer than 24 months . contraindications include primary , tertiary hyperparathyroidism , elevated alkaline phosphatase of uncertain cause , paget 's disease , and osteosarcoma . a study of teriparatide on the effects of calcium were studied and it was seen that following teriparatide 20 mcg / day therapy , the serum calcium levels increased from approximately two hours post - dose , reaching peak levels at 4 - 6 hours post - dose ( median increase 0.4 mg / dl ( 0.1 mmol / l ) ) . serum calcium levels started to decline approximately six hours post - dose , reaching baseline levels at 16 - 24 hours after each dose . after 12 months treatment with teriparatide , > 98% of postmenopausal women or men with primary or hypogonadal osteoporosis had peak serum calcium levels of < 11 mg / dl ( 2.76 mmol / l ) . the median peak serum levels were 9.68 mg / dl ( 2.42 mmol / l ) in postmenopausal women with osteoporosis and 9.44 mg / dl ( 2.35 mmol / l ) in men with primary or hypogonadal osteoporosis . sustained hypercalcemia ( calcium levels > 11 mg / dl [ 2.76 mmol / l ] ) was not observed in the studies although teriparatide can improve bone mass when given for the correct indication , it can be disastrous if used injudiciously as in this case . the case presented can not emphasize enough the need to undertake a thorough endocrine evaluation and rule out all secondary causes of osteoporosis before considering a patient for teriparatide therapy . parathyroid disease is a common cause of raised alkaline phosphatase and is associated with elevated to high normal serum calcium . other isolated endocrine causes of raised alkaline phosphatase ( bone - origin ) include ( severe vitamin d deficiency ( osteomalacia ) ; metastatic bone disease ; severe hyperthyroidism ; fluorosis , and paget 's disease ) . baseline serum calcium in excess of 9.5 mg% with an elevated serum parathormone , with a background of a calcium - poor diet , should prompt physicians to consider  normocalcemic primary hyperparathyroidism, as the possible cause for osteoporosis . moreover lack of improvement of osteoporotic symptoms while on teriparatide should be considered as a clue to look for underlying secondary cause of osteoporosis , like  normocalcemic primary hyperparathyroidism as the cause for failure of therapy . the case should serve as a warning to healthcare professionals who use teriparatide that appropriate metabolic evaluation including a parathormone level must be routinely undertaken before instituting teriparatide .
we describe here the case of an elderly female with severe osteoporosis , who presented with a worsening backache , following teriparatide treatment . 
 she was subsequently diagnosed to have normocalcemic primary hyperparathyroidism . before prescribing teriparatide , 
 an appropriate endocrine evaluation must be undertaken by all healthcare physicians ( serum intact parathyroid hormone ( ipth ) level ) , despite having a normal serum calcium . 
 normocalcemic hyperparathyroidism should be considered as an important alternate cause for osteoporosis .