This study investigates the effectiveness of parathyroid hormone (PTH) in combination with
alendronate, a standard treatment for osteoporosis that blocks or reduces bone loss. We are
using alendronate because it may help protect patients against any possible harmful effects
of PTH in cortical bone such as the long bones or hip. We are testing two different
treatment schedules of PTH-one in which we give PTH daily and one in which we give PTH for 3
out of every 6 months in a cyclical fashion. The entire study is 21 months long; the active
treatment period is 18 months with a 6-month followup period.
The main effects we will look for in this study are changes in body chemicals that are signs
of bone formation or bone breakdown, and changes in bone density throughout the skeleton. We
will randomly assign all study participants, who are women aged 50 and over, to either stay
on alendronate alone, receive daily continuous PTH plus alendronate, or receive daily PTH
for 3 months out of every 6 for a total of three separate 3-month cycles of PTH plus daily
Osteoporosis is a significant disease because it increases the risk of fractures throughout
the skeleton, most importantly in the spine and hip regions. The current medications for
osteoporosis, which include estrogens, bisphosphonates, raloxifene, and calcitonin, all
primarily prevent bone loss, although each may be associated with small bone gains. Another
class of drugs, the anabolic drugs, will increase bone formation more substantially, leading
to bigger gains in bone mass. One of these, sodium fluoride, clearly increases bone mass but
may or may not reduce fracture risk. Another bone-forming agent is human parathyroid hormone
(PTH). We and others have demonstrated substantial bone mass gains as well as a reduction in
vertebral fracture with the use of PTH administered by daily subcutaneous injection.
The current study seeks to capitalize on the knowledge gleaned about PTH-induced stimulation
of bone formation prior to resorption in subjects on antiresorptive therapy such as estrogen
or alendronate. In this protocol we have chosen to give PTH by daily subcutaneous injection
in the presence of alendronate. We have already shown that with 6 weeks of daily
subcutaneous h(1-34)PTH 400 U/day in patients on established alendronate, biochemical
indicators of bone formation are substantially increased (30-60 percent), with no
stimulation of resorption over this time frame.
We hypothesize that, over 3 months, the combination of PTH plus alendronate will, like the
combination of PTH plus hormone replacement therapy, result in increments in bone formation
exceeding those of bone resorption. We also theorize that this biochemical profile will be
reflected in a greater effect on bone mass than during therapy with alendronate alone, when
both formation and resorption are elevated. Furthermore, we believe that the changes over
the first 3 months can be repeated over additional discrete 3-months cycles after bone
turnover returns to baseline.
Therefore, we plan to study the difference in bone mass and biochemical indicators of bone
turnover when, in the presence of established alendronate therapy, we give PTH by daily
subcutaneous injection continuously for 15 months (in which bone resorption is elevated
substantially for more than half of the time) versus discontinuously in three discrete
3-month cycles (in which bone formation will dramatically exceed bone resorption for the
entire treatment period).
The candidates for this study are postmenopausal women who have osteoporosis defined by
either bone density and/or prior osteoporotic fracture occurrence and, in addition, have
used alendronate for at least 18 months prior to entering into the study. Patients must be
over the age of 50.
The entire study is 21 months long; the active treatment period is 18 months with a 6- month
followup period. The primary outcomes in this study are biochemistry and bone density
throughout the skeleton. We will randomly assign all participants to either remain on
alendronate alone, receive daily continuous PTH plus alendronate, or receive daily PTH for 3
months out of every 6, for a total of three separate 3-month cycles of PTH, both with PTH
given in addition to daily or weekly alendronate.
- Approximately 140 postmenopausal women, over 50, who have been on alendronate (at
least 35 mg/week) for a period of at least 18 months.
- Lumbar spine or hip T-score at the time of recruitment must be equal to or below
- All subjects must have primary osteoporosis.
- Subjects cannot be on any other medications known to influence bone metabolism
besides alendronate. Subjects can be on Synthroid if TSH is normal.